Skip to main content
Erschienen in: Cancer Microenvironment 3/2011

01.12.2011 | Original Paper

The PCa Tumor Microenvironment

verfasst von: Joseph L. Sottnik, Jian Zhang, Jill A. Macoska, Evan T. Keller

Erschienen in: Cancer Microenvironment | Ausgabe 3/2011

Einloggen, um Zugang zu erhalten

Abstract

The tumor microenvironment (TME) is a very complex niche that consists of multiple cell types, supportive matrix and soluble factors. Cells in the TME consist of both host cells that are present at tumor site at the onset of tumor growth and cells that are recruited in either response to tumor- or host-derived factors. PCa (PCa) thrives on crosstalk between tumor cells and the TME. Crosstalk results in an orchestrated evolution of both the tumor and microenvironment as the tumor progresses. The TME reacts to PCa-produced soluble factors as well as direct interaction with PCa cells. In return, the TME produces soluble factors, structural support and direct contact interactions that influence the establishment and progression of PCa. In this review, we focus on the host side of the equation to provide a foundation for understanding how different aspects of the TME contribute to PCa progression. We discuss immune effector cells, specialized niches, such as the vascular and bone marrow, and several key protein factors that mediate host effects on PCa. This discussion highlights the concept that the TME offers a potentially very fertile target for PCa therapy.
Literatur
1.
Zurück zum Zitat Keller ET, Li LY (2011) The first Tianjin, China forum on tumor microenvironment. Cancer research 71:310–313PubMed Keller ET, Li LY (2011) The first Tianjin, China forum on tumor microenvironment. Cancer research 71:310–313PubMed
2.
Zurück zum Zitat Niu YN, Xia SJ (2009) Stroma-epithelium crosstalk in prostate cancer. Asian J Androl 11:28–35PubMed Niu YN, Xia SJ (2009) Stroma-epithelium crosstalk in prostate cancer. Asian J Androl 11:28–35PubMed
3.
Zurück zum Zitat Yoneda T, Hiraga T (2005) Crosstalk between cancer cells and bone microenvironment in bone metastasis. Biochem Biophys Res Commun 328:679–687PubMed Yoneda T, Hiraga T (2005) Crosstalk between cancer cells and bone microenvironment in bone metastasis. Biochem Biophys Res Commun 328:679–687PubMed
4.
Zurück zum Zitat Omabe M, Ezeani M (2011) Infection, inflammation and prostate carcinogenesis. Infect Genet Evol. Omabe M, Ezeani M (2011) Infection, inflammation and prostate carcinogenesis. Infect Genet Evol.
5.
Zurück zum Zitat Vasto S, Carruba G, Candore G, Italiano E, Di Bona D, Caruso C (2008) Inflammation and prostate cancer. Future Oncol 4:637–645PubMed Vasto S, Carruba G, Candore G, Italiano E, Di Bona D, Caruso C (2008) Inflammation and prostate cancer. Future Oncol 4:637–645PubMed
6.
Zurück zum Zitat Teng MW, Ritchie DS, Neeson P, Smyth MJ (2010) Biology and clinical observations of regulatory T cells in cancer immunology. Curr Top Microbiol Immunol Teng MW, Ritchie DS, Neeson P, Smyth MJ (2010) Biology and clinical observations of regulatory T cells in cancer immunology. Curr Top Microbiol Immunol
7.
Zurück zum Zitat Miller AM, Lundberg K, Ozenci V, Banham AH, Hellstrom M, Egevad L, Pisa P (2006) CD4 + CD25high T cells are enriched in the tumor and peripheral blood of prostate cancer patients. J Immunol 177:7398–7405PubMed Miller AM, Lundberg K, Ozenci V, Banham AH, Hellstrom M, Egevad L, Pisa P (2006) CD4 + CD25high T cells are enriched in the tumor and peripheral blood of prostate cancer patients. J Immunol 177:7398–7405PubMed
8.
Zurück zum Zitat Sfanos KS, Bruno TC, Maris CH, Xu L, Thoburn CJ, DeMarzo AM, Meeker AK, Isaacs WB, Drake CG (2008) Phenotypic analysis of prostate-infiltrating lymphocytes reveals TH17 and Treg skewing. Clin Cancer Res 14:3254–3261PubMed Sfanos KS, Bruno TC, Maris CH, Xu L, Thoburn CJ, DeMarzo AM, Meeker AK, Isaacs WB, Drake CG (2008) Phenotypic analysis of prostate-infiltrating lymphocytes reveals TH17 and Treg skewing. Clin Cancer Res 14:3254–3261PubMed
9.
Zurück zum Zitat Kiniwa Y, Miyahara Y, Wang HY, Peng W, Peng G, Wheeler TM, Thompson TC, Old LJ, Wang RF (2007) CD8+ Foxp3+ regulatory T cells mediate immunosuppression in prostate cancer. Clin Cancer Res 13:6947–6958PubMed Kiniwa Y, Miyahara Y, Wang HY, Peng W, Peng G, Wheeler TM, Thompson TC, Old LJ, Wang RF (2007) CD8+ Foxp3+ regulatory T cells mediate immunosuppression in prostate cancer. Clin Cancer Res 13:6947–6958PubMed
10.
Zurück zum Zitat Degl’Innocenti E, Grioni M, Capuano G, Jachetti E, Freschi M, Bertilaccio MT, Hess-Michelini R, Doglioni C, Bellone M (2008) Peripheral T-cell tolerance associated with prostate cancer is independent from CD4 + CD25+ regulatory T cells. Cancer Res 68:292–300PubMed Degl’Innocenti E, Grioni M, Capuano G, Jachetti E, Freschi M, Bertilaccio MT, Hess-Michelini R, Doglioni C, Bellone M (2008) Peripheral T-cell tolerance associated with prostate cancer is independent from CD4 + CD25+ regulatory T cells. Cancer Res 68:292–300PubMed
11.
Zurück zum Zitat Yokokawa J, Cereda V, Remondo C, Gulley JL, Arlen PM, Schlom J, Tsang KY (2008) Enhanced functionality of CD4 + CD25(high)FoxP3+ regulatory T cells in the peripheral blood of patients with prostate cancer. Clin Cancer Res 14:1032–1040PubMed Yokokawa J, Cereda V, Remondo C, Gulley JL, Arlen PM, Schlom J, Tsang KY (2008) Enhanced functionality of CD4 + CD25(high)FoxP3+ regulatory T cells in the peripheral blood of patients with prostate cancer. Clin Cancer Res 14:1032–1040PubMed
12.
Zurück zum Zitat Akins EJ, Moore ML, Tang S, Willingham MC, Tooze JA, Dubey P (2010) In situ vaccination combined with androgen ablation and regulatory T-cell depletion reduces castration-resistant tumor burden in prostate-specific pten knockout mice. Cancer Res 70:3473–3482PubMed Akins EJ, Moore ML, Tang S, Willingham MC, Tooze JA, Dubey P (2010) In situ vaccination combined with androgen ablation and regulatory T-cell depletion reduces castration-resistant tumor burden in prostate-specific pten knockout mice. Cancer Res 70:3473–3482PubMed
13.
Zurück zum Zitat Kottke T, Sanchez-Perez L, Diaz RM, Thompson J, Chong H, Harrington K, Calderwood SK, Pulido J, Georgopoulos N, Selby P, Melcher A, Vile R (2007) Induction of hsp70-mediated Th17 autoimmunity can be exploited as immunotherapy for metastatic prostate cancer. Cancer Res 67:11970–11979PubMed Kottke T, Sanchez-Perez L, Diaz RM, Thompson J, Chong H, Harrington K, Calderwood SK, Pulido J, Georgopoulos N, Selby P, Melcher A, Vile R (2007) Induction of hsp70-mediated Th17 autoimmunity can be exploited as immunotherapy for metastatic prostate cancer. Cancer Res 67:11970–11979PubMed
14.
Zurück zum Zitat Derhovanessian E, Adams V, Hahnel K, Groeger A, Pandha H, Ward S, Pawelec G (2009) Pretreatment frequency of circulating IL-17+ CD4+ T-cells, but not Tregs, correlates with clinical response to whole-cell vaccination in prostate cancer patients. Int J Cancer 125:1372–1379PubMed Derhovanessian E, Adams V, Hahnel K, Groeger A, Pandha H, Ward S, Pawelec G (2009) Pretreatment frequency of circulating IL-17+ CD4+ T-cells, but not Tregs, correlates with clinical response to whole-cell vaccination in prostate cancer patients. Int J Cancer 125:1372–1379PubMed
15.
Zurück zum Zitat Lissbrant IF, Stattin P, Wikstrom P, Damber JE, Egevad L, Bergh A (2000) Tumor associated macrophages in human prostate cancer: relation to clinicopathological variables and survival. Int J Oncol 17:445–451PubMed Lissbrant IF, Stattin P, Wikstrom P, Damber JE, Egevad L, Bergh A (2000) Tumor associated macrophages in human prostate cancer: relation to clinicopathological variables and survival. Int J Oncol 17:445–451PubMed
16.
Zurück zum Zitat Nonomura N, Takayama H, Nakayama M, Nakai Y, Kawashima A, Mukai M, Nagahara A, Aozasa K, Tsujimura A (2010) Infiltration of tumour-associated macrophages in prostate biopsy specimens is predictive of disease progression after hormonal therapy for prostate cancer. BJU Int. Nonomura N, Takayama H, Nakayama M, Nakai Y, Kawashima A, Mukai M, Nagahara A, Aozasa K, Tsujimura A (2010) Infiltration of tumour-associated macrophages in prostate biopsy specimens is predictive of disease progression after hormonal therapy for prostate cancer. BJU Int.
17.
Zurück zum Zitat Wong CP, Bray TM, Ho E (2009) Induction of proinflammatory response in prostate cancer epithelial cells by activated macrophages. Cancer Lett 276:38–46PubMed Wong CP, Bray TM, Ho E (2009) Induction of proinflammatory response in prostate cancer epithelial cells by activated macrophages. Cancer Lett 276:38–46PubMed
18.
Zurück zum Zitat Tsai CS, Chen FH, Wang CC, Huang HL, Jung SM, Wu CJ, Lee CC, McBride WH, Chiang CS, Hong JH (2007) Macrophages from irradiated tumors express higher levels of iNOS, arginase-I and COX-2, and promote tumor growth. Int J Radiat Oncol Biol Phys 68:499–507PubMed Tsai CS, Chen FH, Wang CC, Huang HL, Jung SM, Wu CJ, Lee CC, McBride WH, Chiang CS, Hong JH (2007) Macrophages from irradiated tumors express higher levels of iNOS, arginase-I and COX-2, and promote tumor growth. Int J Radiat Oncol Biol Phys 68:499–507PubMed
19.
Zurück zum Zitat Tsagozis P, Eriksson F, Pisa P (2008) Zoledronic acid modulates antitumoral responses of prostate cancer-tumor associated macrophages. Cancer Immunol Immunother 57:1451–1459PubMed Tsagozis P, Eriksson F, Pisa P (2008) Zoledronic acid modulates antitumoral responses of prostate cancer-tumor associated macrophages. Cancer Immunol Immunother 57:1451–1459PubMed
20.
Zurück zum Zitat Halin S, Rudolfsson SH, Van Rooijen N, Bergh A (2009) Extratumoral macrophages promote tumor and vascular growth in an orthotopic rat prostate tumor model. Neoplasia 11:177–186PubMed Halin S, Rudolfsson SH, Van Rooijen N, Bergh A (2009) Extratumoral macrophages promote tumor and vascular growth in an orthotopic rat prostate tumor model. Neoplasia 11:177–186PubMed
21.
Zurück zum Zitat Lindholm PF, Lu Y, Adley BP, Vladislav T, Jovanovic B, Sivapurapu N, Yang XJ, Kajdacsy-Balla A (2010) Role of monocyte-lineage cells in prostate cancer cell invasion and tissue factor expression. Prostate 70:1672–1682PubMed Lindholm PF, Lu Y, Adley BP, Vladislav T, Jovanovic B, Sivapurapu N, Yang XJ, Kajdacsy-Balla A (2010) Role of monocyte-lineage cells in prostate cancer cell invasion and tissue factor expression. Prostate 70:1672–1682PubMed
22.
Zurück zum Zitat Loberg RD, Day LL, Harwood J, Ying C, St John LN, Giles R, Neeley CK, Pienta KJ (2006) CCL2 is a potent regulator of prostate cancer cell migration and proliferation. Neoplasia 8:578–586PubMed Loberg RD, Day LL, Harwood J, Ying C, St John LN, Giles R, Neeley CK, Pienta KJ (2006) CCL2 is a potent regulator of prostate cancer cell migration and proliferation. Neoplasia 8:578–586PubMed
23.
Zurück zum Zitat Lu Y, Xiao G, Galson DL, Nishio Y, Mizokami A, Keller ET, Yao Z, Zhang J (2007) PTHrP-induced MCP-1 production by human bone marrow endothelial cells and osteoblasts promotes osteoclast differentiation and prostate cancer cell proliferation and invasion in vitro. Int J Cancer 121:724–733PubMed Lu Y, Xiao G, Galson DL, Nishio Y, Mizokami A, Keller ET, Yao Z, Zhang J (2007) PTHrP-induced MCP-1 production by human bone marrow endothelial cells and osteoblasts promotes osteoclast differentiation and prostate cancer cell proliferation and invasion in vitro. Int J Cancer 121:724–733PubMed
24.
Zurück zum Zitat Zhang J, Lu Y, Pienta KJ (2010) Multiple roles of chemokine (C-C motif) ligand 2 in promoting prostate cancer growth. J Natl Cancer Inst 102:522–528PubMed Zhang J, Lu Y, Pienta KJ (2010) Multiple roles of chemokine (C-C motif) ligand 2 in promoting prostate cancer growth. J Natl Cancer Inst 102:522–528PubMed
25.
Zurück zum Zitat Muthana M, Giannoudis A, Scott SD, Fang HY, Coffelt SB, Morrow FJ, Murdoch C, Burton J, Cross N, Burke B, Mistry R, Hamdy F, Brown NJ, Georgopoulos L, Hoskin P, Essand M, Lewis CE, Maitland NJ (2011) Use of macrophages to target therapeutic adenovirus to human prostate tumors. Cancer Res 71:1805–1815PubMed Muthana M, Giannoudis A, Scott SD, Fang HY, Coffelt SB, Morrow FJ, Murdoch C, Burton J, Cross N, Burke B, Mistry R, Hamdy F, Brown NJ, Georgopoulos L, Hoskin P, Essand M, Lewis CE, Maitland NJ (2011) Use of macrophages to target therapeutic adenovirus to human prostate tumors. Cancer Res 71:1805–1815PubMed
26.
Zurück zum Zitat Satoh T, Saika T, Ebara S, Kusaka N, Timme TL, Yang G, Wang J, Mouraviev V, Cao G, el MA Fattah, Thompson TC (2003) Macrophages transduced with an adenoviral vector expressing interleukin 12 suppress tumor growth and metastasis in a preclinical metastatic prostate cancer model. Cancer Res 63:7853–7860PubMed Satoh T, Saika T, Ebara S, Kusaka N, Timme TL, Yang G, Wang J, Mouraviev V, Cao G, el MA Fattah, Thompson TC (2003) Macrophages transduced with an adenoviral vector expressing interleukin 12 suppress tumor growth and metastasis in a preclinical metastatic prostate cancer model. Cancer Res 63:7853–7860PubMed
27.
Zurück zum Zitat Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674PubMed Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674PubMed
28.
Zurück zum Zitat Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, Isner JM (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science (New York NY) 275:964–967 Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, Isner JM (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science (New York NY) 275:964–967
29.
Zurück zum Zitat Bertolini F, Shaked Y, Mancuso P, Kerbel RS (2006) The multifaceted circulating endothelial cell in cancer: towards marker and target identification. Nat Rev Cancer 6:835–845PubMed Bertolini F, Shaked Y, Mancuso P, Kerbel RS (2006) The multifaceted circulating endothelial cell in cancer: towards marker and target identification. Nat Rev Cancer 6:835–845PubMed
30.
Zurück zum Zitat Ruzinova MB, Schoer RA, Gerald W, Egan JE, Pandolfi PP, Rafii S, Manova K, Mittal V, Benezra R (2003) Effect of angiogenesis inhibition by Id loss and the contribution of bone-marrow-derived endothelial cells in spontaneous murine tumors. Cancer cell 4:277–289PubMed Ruzinova MB, Schoer RA, Gerald W, Egan JE, Pandolfi PP, Rafii S, Manova K, Mittal V, Benezra R (2003) Effect of angiogenesis inhibition by Id loss and the contribution of bone-marrow-derived endothelial cells in spontaneous murine tumors. Cancer cell 4:277–289PubMed
31.
Zurück zum Zitat Duda DG, Cohen KS, Kozin SV, Perentes JY, Fukumura D, Scadden DT, Jain RK (2006) Evidence for incorporation of bone marrow-derived endothelial cells into perfused blood vessels in tumors. Blood 107:2774–2776PubMed Duda DG, Cohen KS, Kozin SV, Perentes JY, Fukumura D, Scadden DT, Jain RK (2006) Evidence for incorporation of bone marrow-derived endothelial cells into perfused blood vessels in tumors. Blood 107:2774–2776PubMed
32.
Zurück zum Zitat Mancuso P, Antoniotti P, Quarna J, Calleri A, Rabascio C, Tacchetti C, Braidotti P, Wu HK, Zurita AJ, Saronni L, Cheng JB, Shalinsky DR, Heymach JV, Bertolini F (2009) Validation of a standardized method for enumerating circulating endothelial cells and progenitors: flow cytometry and molecular and ultrastructural analyses. Clin Cancer Res 15:267–273PubMed Mancuso P, Antoniotti P, Quarna J, Calleri A, Rabascio C, Tacchetti C, Braidotti P, Wu HK, Zurita AJ, Saronni L, Cheng JB, Shalinsky DR, Heymach JV, Bertolini F (2009) Validation of a standardized method for enumerating circulating endothelial cells and progenitors: flow cytometry and molecular and ultrastructural analyses. Clin Cancer Res 15:267–273PubMed
33.
Zurück zum Zitat Georgiou HD, Namdarian B, Corcoran NM, Costello AJ, Hovens CM (2008) Circulating endothelial cells as biomarkers of prostate cancer. Nature clinical practice 5:445–454PubMed Georgiou HD, Namdarian B, Corcoran NM, Costello AJ, Hovens CM (2008) Circulating endothelial cells as biomarkers of prostate cancer. Nature clinical practice 5:445–454PubMed
34.
Zurück zum Zitat Blann AD, Balakrishnan B, Shantsila E, Ryan P, Lip GY (2010) Endothelial progenitor cells and circulating endothelial cells in early prostate cancer: a comparison with plasma vascular markers. The Prostate Blann AD, Balakrishnan B, Shantsila E, Ryan P, Lip GY (2010) Endothelial progenitor cells and circulating endothelial cells in early prostate cancer: a comparison with plasma vascular markers. The Prostate
35.
Zurück zum Zitat Strijbos MH, Gratama JW, Schmitz PI, Rao C, Onstenk W, Doyle GV, Miller MC, de Wit R, Terstappen LW, Sleijfer S (2010) Circulating endothelial cells, circulating tumour cells, tissue factor, endothelin-1 and overall survival in prostate cancer patients treated with docetaxel. Eur J Cancer 46:2027–2035PubMed Strijbos MH, Gratama JW, Schmitz PI, Rao C, Onstenk W, Doyle GV, Miller MC, de Wit R, Terstappen LW, Sleijfer S (2010) Circulating endothelial cells, circulating tumour cells, tissue factor, endothelin-1 and overall survival in prostate cancer patients treated with docetaxel. Eur J Cancer 46:2027–2035PubMed
36.
Zurück zum Zitat Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS, Dvorak HF (1983) Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science (New York NY) 219:983–985 Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS, Dvorak HF (1983) Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science (New York NY) 219:983–985
37.
Zurück zum Zitat Gille H, Kowalski J, Li B, LeCouter J, Moffat B, Zioncheck TF, Pelletier N, Ferrara N (2001) Analysis of biological effects and signaling properties of Flt-1 (VEGFR-1) and KDR (VEGFR-2). A reassessment using novel receptor-specific vascular endothelial growth factor mutants. J Biol Chem 276:3222–3230PubMed Gille H, Kowalski J, Li B, LeCouter J, Moffat B, Zioncheck TF, Pelletier N, Ferrara N (2001) Analysis of biological effects and signaling properties of Flt-1 (VEGFR-1) and KDR (VEGFR-2). A reassessment using novel receptor-specific vascular endothelial growth factor mutants. J Biol Chem 276:3222–3230PubMed
38.
Zurück zum Zitat Ebos JM, Kerbel RS (2011) Antiangiogenic therapy: impact on invasion, disease progression, and metastasis. Nature reviews. Ebos JM, Kerbel RS (2011) Antiangiogenic therapy: impact on invasion, disease progression, and metastasis. Nature reviews.
39.
Zurück zum Zitat Bono AV, Pannellini T, Liberatore M, Montironi R, Cunico SC, Cheng L, Sasso F, Musiani P, Iezzi M (2010) Sorafenib’s inhibition of prostate cancer growth in transgenic adenocarcinoma mouse prostate mice and its differential effects on endothelial and pericyte growth during tumor angiogenesis. Analytical and quantitative cytology and histology/the International Academy of Cytology [and] American Society of Cytology 32:136–45 Bono AV, Pannellini T, Liberatore M, Montironi R, Cunico SC, Cheng L, Sasso F, Musiani P, Iezzi M (2010) Sorafenib’s inhibition of prostate cancer growth in transgenic adenocarcinoma mouse prostate mice and its differential effects on endothelial and pericyte growth during tumor angiogenesis. Analytical and quantitative cytology and histology/the International Academy of Cytology [and] American Society of Cytology 32:136–45
40.
Zurück zum Zitat Welen K, Jennbacken K, Tesan T, Damber JE (2009) Pericyte coverage decreases invasion of tumour cells into blood vessels in prostate cancer xenografts. Prostate cancer and prostatic diseases 12:41–46PubMed Welen K, Jennbacken K, Tesan T, Damber JE (2009) Pericyte coverage decreases invasion of tumour cells into blood vessels in prostate cancer xenografts. Prostate cancer and prostatic diseases 12:41–46PubMed
41.
Zurück zum Zitat Ozerdem U (2006) Targeting of pericytes diminishes neovascularization and lymphangiogenesis in prostate cancer. Prostate 66:294–304PubMed Ozerdem U (2006) Targeting of pericytes diminishes neovascularization and lymphangiogenesis in prostate cancer. Prostate 66:294–304PubMed
42.
Zurück zum Zitat Cascone T, Herynk MH, Xu L, Du Z, Kadara H, Nilsson MB, Oborn CJ, Park YY, Erez B, Jacoby JJ, Lee JS, Lin HY, Ciardiello F, Herbst RS, Langley RR, Heymach JV (2011) Upregulated stromal EGFR and vascular remodeling in mouse xenograft models of angiogenesis inhibitor-resistant human lung adenocarcinoma. The Journal of clinical investigation. Cascone T, Herynk MH, Xu L, Du Z, Kadara H, Nilsson MB, Oborn CJ, Park YY, Erez B, Jacoby JJ, Lee JS, Lin HY, Ciardiello F, Herbst RS, Langley RR, Heymach JV (2011) Upregulated stromal EGFR and vascular remodeling in mouse xenograft models of angiogenesis inhibitor-resistant human lung adenocarcinoma. The Journal of clinical investigation.
43.
Zurück zum Zitat Edlund M, Sung SY, Chung LW (2004) Modulation of prostate cancer growth in bone microenvironments. J Cell Biochem 91:686–705PubMed Edlund M, Sung SY, Chung LW (2004) Modulation of prostate cancer growth in bone microenvironments. J Cell Biochem 91:686–705PubMed
44.
Zurück zum Zitat Folkman J (1971) Tumor angiogenesis: therapeutic implications. The New England journal of medicine 285:1182–1186PubMed Folkman J (1971) Tumor angiogenesis: therapeutic implications. The New England journal of medicine 285:1182–1186PubMed
45.
Zurück zum Zitat Czyzyk-Krzeska MF, Meller J (2004) von Hippel-Lindau tumor suppressor: not only HIF’s executioner. Trends in molecular medicine 10:146–149PubMed Czyzyk-Krzeska MF, Meller J (2004) von Hippel-Lindau tumor suppressor: not only HIF’s executioner. Trends in molecular medicine 10:146–149PubMed
46.
Zurück zum Zitat Wang J, Wang J, Dai J, Jung Y, Wei CL, Wang Y, Havens AM, Hogg PJ, Keller ET, Pienta KJ, Nor JE, Wang CY, Taichman RS (2007) A glycolytic mechanism regulating an angiogenic switch in prostate cancer. Cancer research 67:149–159PubMed Wang J, Wang J, Dai J, Jung Y, Wei CL, Wang Y, Havens AM, Hogg PJ, Keller ET, Pienta KJ, Nor JE, Wang CY, Taichman RS (2007) A glycolytic mechanism regulating an angiogenic switch in prostate cancer. Cancer research 67:149–159PubMed
47.
Zurück zum Zitat Kai L, Wang J, Ivanovic M, Chung YT, Laskin WB, Schulze-Hoepfner F, Mirochnik Y, Satcher RL Jr, Levenson AS (2011) Targeting prostate cancer angiogenesis through metastasis-associated protein 1 (MTA1). Prostate 71:268–280PubMed Kai L, Wang J, Ivanovic M, Chung YT, Laskin WB, Schulze-Hoepfner F, Mirochnik Y, Satcher RL Jr, Levenson AS (2011) Targeting prostate cancer angiogenesis through metastasis-associated protein 1 (MTA1). Prostate 71:268–280PubMed
48.
Zurück zum Zitat Bruni-Cardoso A, Johnson LC, Vessella RL, Peterson TE, Lynch CC (2010) Osteoclast-derived matrix metalloproteinase-9 directly affects angiogenesis in the prostate tumor-bone microenvironment. Mol Cancer Res 8:459–470PubMed Bruni-Cardoso A, Johnson LC, Vessella RL, Peterson TE, Lynch CC (2010) Osteoclast-derived matrix metalloproteinase-9 directly affects angiogenesis in the prostate tumor-bone microenvironment. Mol Cancer Res 8:459–470PubMed
49.
Zurück zum Zitat Littlepage LE, Sternlicht MD, Rougier N, Phillips J, Gallo E, Yu Y, Williams K, Brenot A, Gordon JI, Werb Z (2010) Matrix metalloproteinases contribute distinct roles in neuroendocrine prostate carcinogenesis, metastasis, and angiogenesis progression. Cancer research 70:2224–2234PubMed Littlepage LE, Sternlicht MD, Rougier N, Phillips J, Gallo E, Yu Y, Williams K, Brenot A, Gordon JI, Werb Z (2010) Matrix metalloproteinases contribute distinct roles in neuroendocrine prostate carcinogenesis, metastasis, and angiogenesis progression. Cancer research 70:2224–2234PubMed
50.
Zurück zum Zitat Morrissey C, True LD, Roudier MP, Coleman IM, Hawley S, Nelson PS, Coleman R, Wang YC, Corey E, Lange PH, Higano CS, Vessella RL (2008) Differential expression of angiogenesis associated genes in prostate cancer bone, liver and lymph node metastases. Clinical & experimental metastasis 25:377–388 Morrissey C, True LD, Roudier MP, Coleman IM, Hawley S, Nelson PS, Coleman R, Wang YC, Corey E, Lange PH, Higano CS, Vessella RL (2008) Differential expression of angiogenesis associated genes in prostate cancer bone, liver and lymph node metastases. Clinical & experimental metastasis 25:377–388
51.
Zurück zum Zitat Emmenegger U, Francia G, Shaked Y, Kerbel RS (2010) Metronomic chemotherapy: principles and lessons learned from applications in the treatment of metastatic prostate cancer. Recent results in cancer research Fortschritte der Krebsforschung 180:165–183 Emmenegger U, Francia G, Shaked Y, Kerbel RS (2010) Metronomic chemotherapy: principles and lessons learned from applications in the treatment of metastatic prostate cancer. Recent results in cancer research Fortschritte der Krebsforschung 180:165–183
52.
Zurück zum Zitat Pasquier E, Kavallaris M, Andre N (2010) Metronomic chemotherapy: new rationale for new directions. Nature reviews 7:455–465PubMed Pasquier E, Kavallaris M, Andre N (2010) Metronomic chemotherapy: new rationale for new directions. Nature reviews 7:455–465PubMed
53.
Zurück zum Zitat Dahut WL, Gulley JL, Arlen PM, Liu Y, Fedenko KM, Steinberg SM, Wright JJ, Parnes H, Chen CC, Jones E, Parker CE, Linehan WM, Figg WD (2004) Randomized phase II trial of docetaxel plus thalidomide in androgen-independent prostate cancer. J Clin Oncol 22:2532–2539PubMed Dahut WL, Gulley JL, Arlen PM, Liu Y, Fedenko KM, Steinberg SM, Wright JJ, Parnes H, Chen CC, Jones E, Parker CE, Linehan WM, Figg WD (2004) Randomized phase II trial of docetaxel plus thalidomide in androgen-independent prostate cancer. J Clin Oncol 22:2532–2539PubMed
54.
Zurück zum Zitat Ning YM, Gulley JL, Arlen PM, Woo S, Steinberg SM, Wright JJ, Parnes HL, Trepel JB, Lee MJ, Kim YS, Sun H, Madan RA, Latham L, Jones E, Chen CC, Figg WD, Dahut WL (2010) Phase II trial of bevacizumab, thalidomide, docetaxel, and prednisone in patients with metastatic castration-resistant prostate cancer. J Clin Oncol 28:2070–2076PubMed Ning YM, Gulley JL, Arlen PM, Woo S, Steinberg SM, Wright JJ, Parnes HL, Trepel JB, Lee MJ, Kim YS, Sun H, Madan RA, Latham L, Jones E, Chen CC, Figg WD, Dahut WL (2010) Phase II trial of bevacizumab, thalidomide, docetaxel, and prednisone in patients with metastatic castration-resistant prostate cancer. J Clin Oncol 28:2070–2076PubMed
55.
Zurück zum Zitat Bianchini D, Zivi A, Sandhu S, de Bono JS (2010) Horizon scanning for novel therapeutics for the treatment of prostate cancer. Ann Oncol 21(Suppl 7):vii43–vii55PubMed Bianchini D, Zivi A, Sandhu S, de Bono JS (2010) Horizon scanning for novel therapeutics for the treatment of prostate cancer. Ann Oncol 21(Suppl 7):vii43–vii55PubMed
56.
Zurück zum Zitat Yu EM, Jain M, Aragon-Ching JB (2010) Angiogenesis inhibitors in prostate cancer therapy. Discovery medicine 10:521–530PubMed Yu EM, Jain M, Aragon-Ching JB (2010) Angiogenesis inhibitors in prostate cancer therapy. Discovery medicine 10:521–530PubMed
57.
Zurück zum Zitat Isaacs JT (2008) Prostate stem cells and benign prostatic hyperplasia. Prostate 68:1025–1034PubMed Isaacs JT (2008) Prostate stem cells and benign prostatic hyperplasia. Prostate 68:1025–1034PubMed
58.
Zurück zum Zitat Coppe JP, Patil CK, Rodier F, Sun Y, Munoz DP, Goldstein J, Nelson PS, Desprez PY, Campisi J (2008) Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol 6:2853–2868PubMed Coppe JP, Patil CK, Rodier F, Sun Y, Munoz DP, Goldstein J, Nelson PS, Desprez PY, Campisi J (2008) Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol 6:2853–2868PubMed
59.
Zurück zum Zitat Untergasser G, Gander R, Lilg C, Lepperdinger G, Plas E, Berger P (2005) Profiling molecular targets of TGF-beta1 in prostate fibroblast-to-myofibroblast transdifferentiation. Mech Ageing Dev 126:59–69PubMed Untergasser G, Gander R, Lilg C, Lepperdinger G, Plas E, Berger P (2005) Profiling molecular targets of TGF-beta1 in prostate fibroblast-to-myofibroblast transdifferentiation. Mech Ageing Dev 126:59–69PubMed
60.
Zurück zum Zitat Tuxhorn JA, Ayala GE, Smith MJ, Smith VC, Dang TD, Rowley DR (2002) Reactive stroma in human prostate cancer: induction of myofibroblast phenotype and extracellular matrix remodeling. Clin Cancer Res 8:2912–2923PubMed Tuxhorn JA, Ayala GE, Smith MJ, Smith VC, Dang TD, Rowley DR (2002) Reactive stroma in human prostate cancer: induction of myofibroblast phenotype and extracellular matrix remodeling. Clin Cancer Res 8:2912–2923PubMed
61.
Zurück zum Zitat Campisi J (2011) Cellular senescence: putting the paradoxes in perspective. Curr Opin Genet Dev 21:107–112PubMed Campisi J (2011) Cellular senescence: putting the paradoxes in perspective. Curr Opin Genet Dev 21:107–112PubMed
62.
Zurück zum Zitat Kuilman T, Michaloglou C, Mooi WJ, Peeper DS (2010) The essence of senescence. Genes Dev 24:2463–2479PubMed Kuilman T, Michaloglou C, Mooi WJ, Peeper DS (2010) The essence of senescence. Genes Dev 24:2463–2479PubMed
63.
Zurück zum Zitat Bavik C, Coleman I, Dean JP, Knudsen B, Plymate S, Nelson PS (2006) The gene expression program of prostate fibroblast senescence modulates neoplastic epithelial cell proliferation through paracrine mechanisms. Cancer Res 66:794–802PubMed Bavik C, Coleman I, Dean JP, Knudsen B, Plymate S, Nelson PS (2006) The gene expression program of prostate fibroblast senescence modulates neoplastic epithelial cell proliferation through paracrine mechanisms. Cancer Res 66:794–802PubMed
64.
Zurück zum Zitat Begley L, Monteleon C, Shah RB, Macdonald JW, Macoska JA (2005) CXCL12 overexpression and secretion by aging fibroblasts enhance human prostate epithelial proliferation in vitro. Aging Cell 4:291–298PubMed Begley L, Monteleon C, Shah RB, Macdonald JW, Macoska JA (2005) CXCL12 overexpression and secretion by aging fibroblasts enhance human prostate epithelial proliferation in vitro. Aging Cell 4:291–298PubMed
65.
Zurück zum Zitat Scotton CJ, Chambers RC (2007) Molecular targets in pulmonary fibrosis: the myofibroblast in focus. Chest 132:1311–1321PubMed Scotton CJ, Chambers RC (2007) Molecular targets in pulmonary fibrosis: the myofibroblast in focus. Chest 132:1311–1321PubMed
66.
Zurück zum Zitat Hinz B, Phan SH, Thannickal VJ, Galli A, Bochaton-Piallat ML, Gabbiani G (2007) The myofibroblast: one function, multiple origins. Am J Pathol 170:1807–1816PubMed Hinz B, Phan SH, Thannickal VJ, Galli A, Bochaton-Piallat ML, Gabbiani G (2007) The myofibroblast: one function, multiple origins. Am J Pathol 170:1807–1816PubMed
67.
Zurück zum Zitat Tuxhorn JA, McAlhany SJ, Dang TD, Ayala GE, Rowley DR (2002) Stromal cells promote angiogenesis and growth of human prostate tumors in a differential reactive stroma (DRS) xenograft model. Cancer Res 62:3298–3307PubMed Tuxhorn JA, McAlhany SJ, Dang TD, Ayala GE, Rowley DR (2002) Stromal cells promote angiogenesis and growth of human prostate tumors in a differential reactive stroma (DRS) xenograft model. Cancer Res 62:3298–3307PubMed
68.
Zurück zum Zitat Schauer IG, Rowley DR (2011) The functional role of reactive stroma in benign prostatic hyperplasia. Differentiation. Schauer IG, Rowley DR (2011) The functional role of reactive stroma in benign prostatic hyperplasia. Differentiation.
69.
Zurück zum Zitat Liao CP, Adisetiyo H, Liang M, Roy-Burman P (2010) Cancer-associated fibroblasts enhance the gland-forming capability of prostate cancer stem cells. Cancer Res 70:7294–7303PubMed Liao CP, Adisetiyo H, Liang M, Roy-Burman P (2010) Cancer-associated fibroblasts enhance the gland-forming capability of prostate cancer stem cells. Cancer Res 70:7294–7303PubMed
70.
Zurück zum Zitat Singh H, Dang TD, Ayala GE, Rowley DR (2004) Transforming growth factor-beta1 induced myofibroblasts regulate LNCaP cell death. J Urol 172:2421–2425PubMed Singh H, Dang TD, Ayala GE, Rowley DR (2004) Transforming growth factor-beta1 induced myofibroblasts regulate LNCaP cell death. J Urol 172:2421–2425PubMed
71.
Zurück zum Zitat Schauer IG, Ressler SJ, Tuxhorn JA, Dang TD, Rowley DR (2008) Elevated epithelial expression of interleukin-8 correlates with myofibroblast reactive stroma in benign prostatic hyperplasia. Urology 72:205–213PubMed Schauer IG, Ressler SJ, Tuxhorn JA, Dang TD, Rowley DR (2008) Elevated epithelial expression of interleukin-8 correlates with myofibroblast reactive stroma in benign prostatic hyperplasia. Urology 72:205–213PubMed
72.
Zurück zum Zitat Schauer IG, Ressler SJ, Rowley DR (2009) Keratinocyte-derived chemokine induces prostate epithelial hyperplasia and reactive stroma in a novel transgenic mouse model. Prostate 69:373–384PubMed Schauer IG, Ressler SJ, Rowley DR (2009) Keratinocyte-derived chemokine induces prostate epithelial hyperplasia and reactive stroma in a novel transgenic mouse model. Prostate 69:373–384PubMed
73.
Zurück zum Zitat Gerdes MJ, Larsen M, Dang TD, Ressler SJ, Tuxhorn JA, Rowley DR (2004) Regulation of rat prostate stromal cell myodifferentiation by androgen and TGF-beta1. Prostate 58:299–307PubMed Gerdes MJ, Larsen M, Dang TD, Ressler SJ, Tuxhorn JA, Rowley DR (2004) Regulation of rat prostate stromal cell myodifferentiation by androgen and TGF-beta1. Prostate 58:299–307PubMed
74.
Zurück zum Zitat Franco OE, Jiang M, Strand DW, Peacock J, Fernandez S, Jackson RS 2nd, Revelo MP, Bhowmick NA, Hayward SW (2011) Altered TGF-beta signaling in a subpopulation of human stromal cells promotes prostatic carcinogenesis. Cancer Res 71:1272–1281PubMed Franco OE, Jiang M, Strand DW, Peacock J, Fernandez S, Jackson RS 2nd, Revelo MP, Bhowmick NA, Hayward SW (2011) Altered TGF-beta signaling in a subpopulation of human stromal cells promotes prostatic carcinogenesis. Cancer Res 71:1272–1281PubMed
75.
Zurück zum Zitat Olumi AF, Grossfeld GD, Hayward SW, Carroll PR, Tlsty TD, Cunha GR (1999) Carcinoma-associated fibroblasts direct tumor progression of initiated human prostatic epithelium. Cancer Res 59:5002–5011PubMed Olumi AF, Grossfeld GD, Hayward SW, Carroll PR, Tlsty TD, Cunha GR (1999) Carcinoma-associated fibroblasts direct tumor progression of initiated human prostatic epithelium. Cancer Res 59:5002–5011PubMed
76.
Zurück zum Zitat Wang J, Levenson AS, Satcher RL Jr (2006) Identification of a unique set of genes altered during cell-cell contact in an in vitro model of prostate cancer bone metastasis. Int J Mol Med 17:849–856PubMed Wang J, Levenson AS, Satcher RL Jr (2006) Identification of a unique set of genes altered during cell-cell contact in an in vitro model of prostate cancer bone metastasis. Int J Mol Med 17:849–856PubMed
77.
Zurück zum Zitat Zhang S, Wang J, Bilen MA, Lin SH, Stupp SI, Satcher RL (2009) Modulation of prostate cancer cell gene expression by cell-to-cell contact with bone marrow stromal cells or osteoblasts. Clin Exp Metastasis 26:993–1004PubMed Zhang S, Wang J, Bilen MA, Lin SH, Stupp SI, Satcher RL (2009) Modulation of prostate cancer cell gene expression by cell-to-cell contact with bone marrow stromal cells or osteoblasts. Clin Exp Metastasis 26:993–1004PubMed
78.
Zurück zum Zitat Festuccia C, Giunciuglio D, Guerra F, Villanova I, Angelucci A, Manduca P, Teti A, Albini A, Bologna M (1999) Osteoblasts modulate secretion of urokinase-type plasminogen activator (uPA) and matrix metalloproteinase-9 (MMP-9) in human prostate cancer cells promoting migration and matrigel invasion. Oncol Res 11:17–31PubMed Festuccia C, Giunciuglio D, Guerra F, Villanova I, Angelucci A, Manduca P, Teti A, Albini A, Bologna M (1999) Osteoblasts modulate secretion of urokinase-type plasminogen activator (uPA) and matrix metalloproteinase-9 (MMP-9) in human prostate cancer cells promoting migration and matrigel invasion. Oncol Res 11:17–31PubMed
79.
Zurück zum Zitat Duivenvoorden WC, Hirte HW, Singh G (1999) Transforming growth factor beta1 acts as an inducer of matrix metalloproteinase expression and activity in human bone-metastasizing cancer cells. Clin Exp Metastasis 17:27–34PubMed Duivenvoorden WC, Hirte HW, Singh G (1999) Transforming growth factor beta1 acts as an inducer of matrix metalloproteinase expression and activity in human bone-metastasizing cancer cells. Clin Exp Metastasis 17:27–34PubMed
80.
Zurück zum Zitat Festuccia C, Bologna M, Gravina GL, Guerra F, Angelucci A, Villanova I, Millimaggi D, Teti A (1999) Osteoblast conditioned media contain TGF-beta1 and modulate the migration of prostate tumor cells and their interactions with extracellular matrix components. Int J Cancer 81:395–403PubMed Festuccia C, Bologna M, Gravina GL, Guerra F, Angelucci A, Villanova I, Millimaggi D, Teti A (1999) Osteoblast conditioned media contain TGF-beta1 and modulate the migration of prostate tumor cells and their interactions with extracellular matrix components. Int J Cancer 81:395–403PubMed
81.
Zurück zum Zitat Chiao JW, Moonga BS, Yang YM, Kancherla R, Mittelman A, Wu-Wong JR, Ahmed T (2000) Endothelin-1 from prostate cancer cells is enhanced by bone contact which blocks osteoclastic bone resorption. Br J Cancer 83:360–365PubMed Chiao JW, Moonga BS, Yang YM, Kancherla R, Mittelman A, Wu-Wong JR, Ahmed T (2000) Endothelin-1 from prostate cancer cells is enhanced by bone contact which blocks osteoclastic bone resorption. Br J Cancer 83:360–365PubMed
82.
Zurück zum Zitat Guise TA, Yin JJ, Mohammad KS (2003) Role of endothelin-1 in osteoblastic bone metastases. Cancer 97:779–784PubMed Guise TA, Yin JJ, Mohammad KS (2003) Role of endothelin-1 in osteoblastic bone metastases. Cancer 97:779–784PubMed
83.
Zurück zum Zitat Akhavan A, McHugh KH, Guruli G, Bies RR, Zamboni WC, Strychor SA, Nelson JB, Pflug BR (2006) Endothelin receptor A blockade enhances taxane effects in prostate cancer. Neoplasia 8:725–732PubMed Akhavan A, McHugh KH, Guruli G, Bies RR, Zamboni WC, Strychor SA, Nelson JB, Pflug BR (2006) Endothelin receptor A blockade enhances taxane effects in prostate cancer. Neoplasia 8:725–732PubMed
84.
Zurück zum Zitat Weydert CJ, Esser AK, Mejia RA, Drake JM, Barnes JM, Henry MD (2009) Endothelin-1 inhibits prostate cancer growth in vivo through vasoconstriction of tumor-feeding arterioles. Cancer Biol Ther 8:720–729PubMed Weydert CJ, Esser AK, Mejia RA, Drake JM, Barnes JM, Henry MD (2009) Endothelin-1 inhibits prostate cancer growth in vivo through vasoconstriction of tumor-feeding arterioles. Cancer Biol Ther 8:720–729PubMed
85.
Zurück zum Zitat Murphy G (2005) Atrasentan for metastatic hormone refractory prostate cancer. Issues Emerg Health Technol:1–4 Murphy G (2005) Atrasentan for metastatic hormone refractory prostate cancer. Issues Emerg Health Technol:1–4
86.
Zurück zum Zitat Nelson JB, Love W, Chin JL, Saad F, Schulman CC, Sleep DJ, Qian J, Steinberg J, Carducci M (2008) Phase 3, randomized, controlled trial of atrasentan in patients with nonmetastatic, hormone-refractory prostate cancer. Cancer 113:2478–2487PubMed Nelson JB, Love W, Chin JL, Saad F, Schulman CC, Sleep DJ, Qian J, Steinberg J, Carducci M (2008) Phase 3, randomized, controlled trial of atrasentan in patients with nonmetastatic, hormone-refractory prostate cancer. Cancer 113:2478–2487PubMed
87.
Zurück zum Zitat Shepard DR, Dreicer R (2010) Zibotentan for the treatment of castrate-resistant prostate cancer. Expert Opin Investig Drugs 19:899–908PubMed Shepard DR, Dreicer R (2010) Zibotentan for the treatment of castrate-resistant prostate cancer. Expert Opin Investig Drugs 19:899–908PubMed
88.
Zurück zum Zitat Fu Z, Dozmorov IM, Keller ET (2002) Osteoblasts produce soluble factors that induce a gene expression pattern in non-metastatic prostate cancer cells, similar to that found in bone metastatic prostate cancer cells. Prostate 51:10–20PubMed Fu Z, Dozmorov IM, Keller ET (2002) Osteoblasts produce soluble factors that induce a gene expression pattern in non-metastatic prostate cancer cells, similar to that found in bone metastatic prostate cancer cells. Prostate 51:10–20PubMed
89.
Zurück zum Zitat Reyes-Moreno C, Sourla A, Choki I, Doillon C, Koutsilieris M (1998) Osteoblast-derived survival factors protect PC-3 human prostate cancer cells from adriamycin apoptosis. Urology 52:341–347PubMed Reyes-Moreno C, Sourla A, Choki I, Doillon C, Koutsilieris M (1998) Osteoblast-derived survival factors protect PC-3 human prostate cancer cells from adriamycin apoptosis. Urology 52:341–347PubMed
90.
Zurück zum Zitat Sun YX, Schneider A, Jung Y, Wang J, Dai J, Cook K, Osman NI, Koh-Paige AJ, Shim H, Pienta KJ, Keller ET, McCauley LK, Taichman RS (2005) Skeletal localization and neutralization of the SDF-1(CXCL12)/CXCR4 axis blocks prostate cancer metastasis and growth in osseous sites in vivo. J Bone Miner Res 20:318–329PubMed Sun YX, Schneider A, Jung Y, Wang J, Dai J, Cook K, Osman NI, Koh-Paige AJ, Shim H, Pienta KJ, Keller ET, McCauley LK, Taichman RS (2005) Skeletal localization and neutralization of the SDF-1(CXCL12)/CXCR4 axis blocks prostate cancer metastasis and growth in osseous sites in vivo. J Bone Miner Res 20:318–329PubMed
91.
Zurück zum Zitat Shiozawa Y, Pedersen EA, Havens AM, Jung Y, Mishra A, Joseph J, Kim JK, Patel LR, Ying C, Ziegler AM, Pienta MJ, Song J, Wang J, Loberg RD, Krebsbach PH, Pienta KJ, Taichman RS (2011) Human prostate cancer metastases target the hematopoietic stem cell niche to establish footholds in mouse bone marrow. J Clin Invest. Shiozawa Y, Pedersen EA, Havens AM, Jung Y, Mishra A, Joseph J, Kim JK, Patel LR, Ying C, Ziegler AM, Pienta MJ, Song J, Wang J, Loberg RD, Krebsbach PH, Pienta KJ, Taichman RS (2011) Human prostate cancer metastases target the hematopoietic stem cell niche to establish footholds in mouse bone marrow. J Clin Invest.
92.
Zurück zum Zitat Zhu X, Humphrey PA (2000) Overexpression and regulation of expression of scatter factor/hepatocyte growth factor in prostatic carcinoma. Urology 56:1071–1074PubMed Zhu X, Humphrey PA (2000) Overexpression and regulation of expression of scatter factor/hepatocyte growth factor in prostatic carcinoma. Urology 56:1071–1074PubMed
93.
Zurück zum Zitat Humphrey PA, Zhu X, Zarnegar R, Swanson PE, Ratliff TL, Vollmer RT, Day ML (1995) Hepatocyte growth factor and its receptor (c-MET) in prostatic carcinoma. Am J Pathol 147:386–396PubMed Humphrey PA, Zhu X, Zarnegar R, Swanson PE, Ratliff TL, Vollmer RT, Day ML (1995) Hepatocyte growth factor and its receptor (c-MET) in prostatic carcinoma. Am J Pathol 147:386–396PubMed
94.
Zurück zum Zitat Naughton M, Picus J, Zhu X, Catalona WJ, Vollmer RT, Humphrey PA (2001) Scatter factor-hepatocyte growth factor elevation in the serum of patients with prostate cancer. J Urol 165:1325–1328PubMed Naughton M, Picus J, Zhu X, Catalona WJ, Vollmer RT, Humphrey PA (2001) Scatter factor-hepatocyte growth factor elevation in the serum of patients with prostate cancer. J Urol 165:1325–1328PubMed
95.
Zurück zum Zitat Hashem M, Essam T (2005) Hepatocyte growth factor as a tumor marker in the serum of patients with prostate cancer. J Egypt Natl Canc Inst 17:114–120PubMed Hashem M, Essam T (2005) Hepatocyte growth factor as a tumor marker in the serum of patients with prostate cancer. J Egypt Natl Canc Inst 17:114–120PubMed
96.
Zurück zum Zitat Gupta A, Karakiewicz PI, Roehrborn CG, Lotan Y, Zlotta AR, Shariat SF (2008) Predictive value of plasma hepatocyte growth factor/scatter factor levels in patients with clinically localized prostate cancer. Clin Cancer Res 14:7385–7390PubMed Gupta A, Karakiewicz PI, Roehrborn CG, Lotan Y, Zlotta AR, Shariat SF (2008) Predictive value of plasma hepatocyte growth factor/scatter factor levels in patients with clinically localized prostate cancer. Clin Cancer Res 14:7385–7390PubMed
97.
Zurück zum Zitat Maeda A, Nakashiro K, Hara S, Sasaki T, Miwa Y, Tanji N, Yokoyama M, Hamakawa H, Oyasu R (2006) Inactivation of AR activates HGF/c-Met system in human prostatic carcinoma cells. Biochem Biophys Res Commun 347:1158–1165PubMed Maeda A, Nakashiro K, Hara S, Sasaki T, Miwa Y, Tanji N, Yokoyama M, Hamakawa H, Oyasu R (2006) Inactivation of AR activates HGF/c-Met system in human prostatic carcinoma cells. Biochem Biophys Res Commun 347:1158–1165PubMed
98.
Zurück zum Zitat Pisters LL, Troncoso P, Zhau HE, Li W, von Eschenbach AC, Chung LW (1995) c-met proto-oncogene expression in benign and malignant human prostate tissues. J Urol 154:293–298PubMed Pisters LL, Troncoso P, Zhau HE, Li W, von Eschenbach AC, Chung LW (1995) c-met proto-oncogene expression in benign and malignant human prostate tissues. J Urol 154:293–298PubMed
99.
Zurück zum Zitat Wang Y, Yue D, Li K, Liu YL, Ren CS, Wang P (2010) The role of TRPC6 in HGF-induced cell proliferation of human prostate cancer DU145 and PC3 cells. Asian J Androl 12:841–852PubMed Wang Y, Yue D, Li K, Liu YL, Ren CS, Wang P (2010) The role of TRPC6 in HGF-induced cell proliferation of human prostate cancer DU145 and PC3 cells. Asian J Androl 12:841–852PubMed
100.
Zurück zum Zitat Nishimura K, Kitamura M, Takada S, Nonomura N, Tsujimura A, Matsumiya K, Miki T, Matsumoto K, Okuyama A (1998) Regulation of invasive potential of human prostate cancer cell lines by hepatocyte growth factor. Int J Urol 5:276–281PubMed Nishimura K, Kitamura M, Takada S, Nonomura N, Tsujimura A, Matsumiya K, Miki T, Matsumoto K, Okuyama A (1998) Regulation of invasive potential of human prostate cancer cell lines by hepatocyte growth factor. Int J Urol 5:276–281PubMed
101.
Zurück zum Zitat Nishimura K, Kitamura M, Miura H, Nonomura N, Takada S, Takahara S, Matsumoto K, Nakamura T, Matsumiya K (1999) Prostate stromal cell-derived hepatocyte growth factor induces invasion of prostate cancer cell line DU145 through tumor-stromal interaction. Prostate 41:145–153PubMed Nishimura K, Kitamura M, Miura H, Nonomura N, Takada S, Takahara S, Matsumoto K, Nakamura T, Matsumiya K (1999) Prostate stromal cell-derived hepatocyte growth factor induces invasion of prostate cancer cell line DU145 through tumor-stromal interaction. Prostate 41:145–153PubMed
102.
Zurück zum Zitat Miura H, Nishimura K, Tsujimura A, Matsumiya K, Matsumoto K, Nakamura T, Okuyama A (2001) Effects of hepatocyte growth factor on E-cadherin-mediated cell-cell adhesion in DU145 prostate cancer cells. Urology 58:1064–1069PubMed Miura H, Nishimura K, Tsujimura A, Matsumiya K, Matsumoto K, Nakamura T, Okuyama A (2001) Effects of hepatocyte growth factor on E-cadherin-mediated cell-cell adhesion in DU145 prostate cancer cells. Urology 58:1064–1069PubMed
103.
Zurück zum Zitat Steffan JJ, Williams BC, Welbourne T, Cardelli JA (2010) HGF-induced invasion by prostate tumor cells requires anterograde lysosome trafficking and activity of Na + −H + exchangers. J Cell Sci 123:1151–1159PubMed Steffan JJ, Williams BC, Welbourne T, Cardelli JA (2010) HGF-induced invasion by prostate tumor cells requires anterograde lysosome trafficking and activity of Na + −H + exchangers. J Cell Sci 123:1151–1159PubMed
104.
Zurück zum Zitat Ye L, Lewis-Russell JM, Davies G, Sanders AJ, Kynaston H, Jiang WG (2007) Hepatocyte growth factor up-regulates the expression of the bone morphogenetic protein (BMP) receptors, BMPR-IB and BMPR-II, in human prostate cancer cells. Int J Oncol 30:521–529PubMed Ye L, Lewis-Russell JM, Davies G, Sanders AJ, Kynaston H, Jiang WG (2007) Hepatocyte growth factor up-regulates the expression of the bone morphogenetic protein (BMP) receptors, BMPR-IB and BMPR-II, in human prostate cancer cells. Int J Oncol 30:521–529PubMed
105.
Zurück zum Zitat Tsuka H, Mori H, Li B, Kanamaru H, Matsukawa S, Okada K (1998) Expression of c-MET/HGF receptor mRNA and protein in human non-malignant and malignant prostate tissues. Int J Oncol 13:927–934PubMed Tsuka H, Mori H, Li B, Kanamaru H, Matsukawa S, Okada K (1998) Expression of c-MET/HGF receptor mRNA and protein in human non-malignant and malignant prostate tissues. Int J Oncol 13:927–934PubMed
106.
Zurück zum Zitat Davies G, Mason MD, Martin TA, Parr C, Watkins G, Lane J, Matsumoto K, Nakamura T, Jiang WG (2003) The HGF/SF antagonist NK4 reverses fibroblast- and HGF-induced prostate tumor growth and angiogenesis in vivo. Int J Cancer 106:348–354PubMed Davies G, Mason MD, Martin TA, Parr C, Watkins G, Lane J, Matsumoto K, Nakamura T, Jiang WG (2003) The HGF/SF antagonist NK4 reverses fibroblast- and HGF-induced prostate tumor growth and angiogenesis in vivo. Int J Cancer 106:348–354PubMed
107.
Zurück zum Zitat Dai Y, Siemann DW (2010) BMS-777607, a small-molecule met kinase inhibitor, suppresses hepatocyte growth factor-stimulated prostate cancer metastatic phenotype in vitro. Mol Cancer Ther 9:1554–1561PubMed Dai Y, Siemann DW (2010) BMS-777607, a small-molecule met kinase inhibitor, suppresses hepatocyte growth factor-stimulated prostate cancer metastatic phenotype in vitro. Mol Cancer Ther 9:1554–1561PubMed
108.
Zurück zum Zitat Elnagar AY, Sylvester PW, El Sayed KA (2011) (−)-Oleocanthal as a c-Met inhibitor for the control of metastatic breast and prostate cancers. Planta Med Elnagar AY, Sylvester PW, El Sayed KA (2011) (−)-Oleocanthal as a c-Met inhibitor for the control of metastatic breast and prostate cancers. Planta Med
109.
Zurück zum Zitat Culig Z, Puhr M (2011) Interleukin-6: a multifunctional targetable cytokine in human prostate cancer. Mol Cell Endocrinol Culig Z, Puhr M (2011) Interleukin-6: a multifunctional targetable cytokine in human prostate cancer. Mol Cell Endocrinol
110.
Zurück zum Zitat George DJ, Halabi S, Shepard TF, Sanford B, Vogelzang NJ, Small EJ, Kantoff PW (2005) The prognostic significance of plasma interleukin-6 levels in patients with metastatic hormone-refractory prostate cancer: results from cancer and leukemia group B 9480. Clin Cancer Res 11:1815–1820PubMed George DJ, Halabi S, Shepard TF, Sanford B, Vogelzang NJ, Small EJ, Kantoff PW (2005) The prognostic significance of plasma interleukin-6 levels in patients with metastatic hormone-refractory prostate cancer: results from cancer and leukemia group B 9480. Clin Cancer Res 11:1815–1820PubMed
111.
Zurück zum Zitat Alcover J, Filella X, Luque P, Molina R, Izquierdo L, Auge JM, Alcaraz A (2010) Prognostic value of IL-6 in localized prostatic cancer. Anticancer Res 30:4369–4372PubMed Alcover J, Filella X, Luque P, Molina R, Izquierdo L, Auge JM, Alcaraz A (2010) Prognostic value of IL-6 in localized prostatic cancer. Anticancer Res 30:4369–4372PubMed
112.
Zurück zum Zitat Stark JR, Li H, Kraft P, Kurth T, Giovannucci EL, Stampfer MJ, Ma J, Mucci LA (2009) Circulating prediagnostic interleukin-6 and C-reactive protein and prostate cancer incidence and mortality. International journal of cancer Journal international du cancer 124:2683–2689PubMed Stark JR, Li H, Kraft P, Kurth T, Giovannucci EL, Stampfer MJ, Ma J, Mucci LA (2009) Circulating prediagnostic interleukin-6 and C-reactive protein and prostate cancer incidence and mortality. International journal of cancer Journal international du cancer 124:2683–2689PubMed
113.
Zurück zum Zitat Chung TD, Yu JJ, Spiotto MT, Bartkowski M, Simons JW (1999) Characterization of the role of IL-6 in the progression of prostate cancer. Prostate 38:199–207PubMed Chung TD, Yu JJ, Spiotto MT, Bartkowski M, Simons JW (1999) Characterization of the role of IL-6 in the progression of prostate cancer. Prostate 38:199–207PubMed
114.
Zurück zum Zitat Alberti C (2010) Neuroendocrine differentiation in prostate carcinoma: focusing on its pathophysiologic mechanisms and pathological features. G Chir 31:568–574PubMed Alberti C (2010) Neuroendocrine differentiation in prostate carcinoma: focusing on its pathophysiologic mechanisms and pathological features. G Chir 31:568–574PubMed
115.
Zurück zum Zitat Lee GT, Kwon SJ, Lee JH, Jeon SS, Jang KT, Choi HY, Lee HM, Kim WJ, Lee DH, Kim IY (2011) Macrophages induce neuroendocrine differentiation of prostate cancer cells via BMP6-IL6 Loop. The Prostate Lee GT, Kwon SJ, Lee JH, Jeon SS, Jang KT, Choi HY, Lee HM, Kim WJ, Lee DH, Kim IY (2011) Macrophages induce neuroendocrine differentiation of prostate cancer cells via BMP6-IL6 Loop. The Prostate
116.
Zurück zum Zitat Smith ND, Schulze-Hoepfner FT, Veliceasa D, Filleur S, Shareef S, Huang L, Huang XM, Volpert OV (2008) Pigment epithelium-derived factor and interleukin-6 control prostate neuroendocrine differentiation via feed-forward mechanism. J Urol 179:2427–2434PubMed Smith ND, Schulze-Hoepfner FT, Veliceasa D, Filleur S, Shareef S, Huang L, Huang XM, Volpert OV (2008) Pigment epithelium-derived factor and interleukin-6 control prostate neuroendocrine differentiation via feed-forward mechanism. J Urol 179:2427–2434PubMed
117.
Zurück zum Zitat Okamoto M, Lee C, Oyasu R (1997) Autocrine effect of androgen on proliferation of an androgen-responsive prostatic carcinoma cell line, LNCaP: role of interleukin-6. Endocrinology 138:5071–5074PubMed Okamoto M, Lee C, Oyasu R (1997) Autocrine effect of androgen on proliferation of an androgen-responsive prostatic carcinoma cell line, LNCaP: role of interleukin-6. Endocrinology 138:5071–5074PubMed
118.
Zurück zum Zitat Qiu Y, Ravi L, Kung HJ (1998) Requirement of ErbB2 for signalling by interleukin-6 in prostate carcinoma cells. Nature 393:83–85PubMed Qiu Y, Ravi L, Kung HJ (1998) Requirement of ErbB2 for signalling by interleukin-6 in prostate carcinoma cells. Nature 393:83–85PubMed
119.
Zurück zum Zitat Wallner L, Dai J, Escara-Wilke J, Zhang J, Yao Z, Lu Y, Trikha M, Nemeth JA, Zaki MH, Keller ET (2006) Inhibition of interleukin-6 with CNTO328, an anti-interleukin-6 monoclonal antibody, inhibits conversion of androgen-dependent prostate cancer to an androgen-independent phenotype in orchiectomized mice. Cancer Res 66:3087–3095PubMed Wallner L, Dai J, Escara-Wilke J, Zhang J, Yao Z, Lu Y, Trikha M, Nemeth JA, Zaki MH, Keller ET (2006) Inhibition of interleukin-6 with CNTO328, an anti-interleukin-6 monoclonal antibody, inhibits conversion of androgen-dependent prostate cancer to an androgen-independent phenotype in orchiectomized mice. Cancer Res 66:3087–3095PubMed
120.
Zurück zum Zitat Culig Z, Steiner H, Bartsch G, Hobisch A (2005) Interleukin-6 regulation of prostate cancer cell growth. J Cell Biochem 95:497–505PubMed Culig Z, Steiner H, Bartsch G, Hobisch A (2005) Interleukin-6 regulation of prostate cancer cell growth. J Cell Biochem 95:497–505PubMed
121.
Zurück zum Zitat Corey E, Quinn JE, Buhler KR, Nelson PS, Macoska JA, True LD, Vessella RL (2003) LuCaP 35: a new model of prostate cancer progression to androgen independence. Prostate 55:239–246PubMed Corey E, Quinn JE, Buhler KR, Nelson PS, Macoska JA, True LD, Vessella RL (2003) LuCaP 35: a new model of prostate cancer progression to androgen independence. Prostate 55:239–246PubMed
122.
Zurück zum Zitat Smith PC, Keller ET (2001) Anti-interleukin-6 monoclonal antibody induces regression of human prostate cancer xenografts in nude mice. Prostate 48:47–53PubMed Smith PC, Keller ET (2001) Anti-interleukin-6 monoclonal antibody induces regression of human prostate cancer xenografts in nude mice. Prostate 48:47–53PubMed
123.
Zurück zum Zitat Chung TD, Yu JJ, Kong TA, Spiotto MT, Lin JM (2000) Interleukin-6 activates phosphatidylinositol-3 kinase, which inhibits apoptosis in human prostate cancer cell lines. Prostate 42:1–7PubMed Chung TD, Yu JJ, Kong TA, Spiotto MT, Lin JM (2000) Interleukin-6 activates phosphatidylinositol-3 kinase, which inhibits apoptosis in human prostate cancer cell lines. Prostate 42:1–7PubMed
124.
Zurück zum Zitat Lee SO, Lou W, Johnson CS, Trump DL, Gao AC (2004) Interleukin-6 protects LNCaP cells from apoptosis induced by androgen deprivation through the Stat3 pathway. Prostate 60:178–186PubMed Lee SO, Lou W, Johnson CS, Trump DL, Gao AC (2004) Interleukin-6 protects LNCaP cells from apoptosis induced by androgen deprivation through the Stat3 pathway. Prostate 60:178–186PubMed
125.
Zurück zum Zitat Rojas A, Liu G, Coleman I, Nelson PS, Zhang M, Dash R, Fisher PB, Plymate SR, Wu JD (2011) IL-6 promotes prostate tumorigenesis and progression through autocrine cross-activation of IGF-IR. Oncogene. Rojas A, Liu G, Coleman I, Nelson PS, Zhang M, Dash R, Fisher PB, Plymate SR, Wu JD (2011) IL-6 promotes prostate tumorigenesis and progression through autocrine cross-activation of IGF-IR. Oncogene.
126.
Zurück zum Zitat Roca H, Varsos ZS, Sud S, Craig MJ, Ying C, Pienta KJ (2009) CCL2 and interleukin-6 promote survival of human CD11b + peripheral blood mononuclear cells and induce M2-type macrophage polarization. J Biol Chem 284:34342–34354PubMed Roca H, Varsos ZS, Sud S, Craig MJ, Ying C, Pienta KJ (2009) CCL2 and interleukin-6 promote survival of human CD11b + peripheral blood mononuclear cells and induce M2-type macrophage polarization. J Biol Chem 284:34342–34354PubMed
127.
Zurück zum Zitat Dorff TB, Goldman B, Pinski JK, Mack PC, Lara PN Jr, Van Veldhuizen PJ Jr, Quinn DI, Vogelzang NJ, Thompson IM Jr, Hussain MH (2010) Clinical and correlative results of SWOG S0354: a phase II trial of CNTO328 (siltuximab), a monoclonal antibody against interleukin-6, in chemotherapy-pretreated patients with castration-resistant prostate cancer. Clin Cancer Res 16:3028–3034PubMed Dorff TB, Goldman B, Pinski JK, Mack PC, Lara PN Jr, Van Veldhuizen PJ Jr, Quinn DI, Vogelzang NJ, Thompson IM Jr, Hussain MH (2010) Clinical and correlative results of SWOG S0354: a phase II trial of CNTO328 (siltuximab), a monoclonal antibody against interleukin-6, in chemotherapy-pretreated patients with castration-resistant prostate cancer. Clin Cancer Res 16:3028–3034PubMed
128.
Zurück zum Zitat Cavarretta IT, Neuwirt H, Zaki MH, Steiner H, Hobisch A, Nemeth JA, Culig Z (2008) Mcl-1 is regulated by IL-6 and mediates the survival activity of the cytokine in a model of late stage prostate carcinoma. Adv Exp Med Biol 617:547–555PubMed Cavarretta IT, Neuwirt H, Zaki MH, Steiner H, Hobisch A, Nemeth JA, Culig Z (2008) Mcl-1 is regulated by IL-6 and mediates the survival activity of the cytokine in a model of late stage prostate carcinoma. Adv Exp Med Biol 617:547–555PubMed
129.
Zurück zum Zitat Sabbota AL, Kim HR, Zhe X, Fridman R, Bonfil RD, Cher ML (2010) Shedding of RANKL by tumor-associated MT1-MMP activates Src-dependent prostate cancer cell migration. Cancer research 70:5558–5566PubMed Sabbota AL, Kim HR, Zhe X, Fridman R, Bonfil RD, Cher ML (2010) Shedding of RANKL by tumor-associated MT1-MMP activates Src-dependent prostate cancer cell migration. Cancer research 70:5558–5566PubMed
130.
Zurück zum Zitat Yasuda H, Shima N, Nakagawa N, Mochizuki SI, Yano K, Fujise N, Sato Y, Goto M, Yamaguchi K, Kuriyama M, Kanno T, Murakami A, Tsuda E, Morinaga T, Higashio K (1998) Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro. Endocrinology 139:1329–1337PubMed Yasuda H, Shima N, Nakagawa N, Mochizuki SI, Yano K, Fujise N, Sato Y, Goto M, Yamaguchi K, Kuriyama M, Kanno T, Murakami A, Tsuda E, Morinaga T, Higashio K (1998) Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro. Endocrinology 139:1329–1337PubMed
131.
Zurück zum Zitat Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, Elliott R, Colombero A, Elliott G, Scully S, Hsu H, Sullivan J, Hawkins N, Davy E, Capparelli C, Eli A, Qian YX, Kaufman S, Sarosi I, Shalhoub V, Senaldi G, Guo J, Delaney J, Boyle WJ (1998) Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 93:165–176PubMed Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, Elliott R, Colombero A, Elliott G, Scully S, Hsu H, Sullivan J, Hawkins N, Davy E, Capparelli C, Eli A, Qian YX, Kaufman S, Sarosi I, Shalhoub V, Senaldi G, Guo J, Delaney J, Boyle WJ (1998) Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 93:165–176PubMed
132.
Zurück zum Zitat Dougall WC, Glaccum M, Charrier K, Rohrbach K, Brasel K, De Smedt T, Daro E, Smith J, Tometsko ME, Maliszewski CR, Armstrong A, Shen V, Bain S, Cosman D, Anderson D, Morrissey PJ, Peschon JJ, Schuh J (1999) RANK is essential for osteoclast and lymph node development. Genes Dev 13:2412–2424PubMed Dougall WC, Glaccum M, Charrier K, Rohrbach K, Brasel K, De Smedt T, Daro E, Smith J, Tometsko ME, Maliszewski CR, Armstrong A, Shen V, Bain S, Cosman D, Anderson D, Morrissey PJ, Peschon JJ, Schuh J (1999) RANK is essential for osteoclast and lymph node development. Genes Dev 13:2412–2424PubMed
133.
Zurück zum Zitat Kong YY, Boyle WJ, Penninger JM (1999) Osteoprotegerin ligand: a common link between osteoclastogenesis, lymph node formation and lymphocyte development. Immunol Cell Biol 77:188–193PubMed Kong YY, Boyle WJ, Penninger JM (1999) Osteoprotegerin ligand: a common link between osteoclastogenesis, lymph node formation and lymphocyte development. Immunol Cell Biol 77:188–193PubMed
134.
Zurück zum Zitat Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Luthy R, Nguyen HQ, Wooden S, Bennett L, Boone T, Shimamoto G, DeRose M, Elliott R, Colombero A, Tan HL, Trail G, Sullivan J, Davy E, Bucay N, Renshaw-Gegg L, Hughes TM, Hill D, Pattison W, Campbell P, Boyle WJ et al (1997) Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 89:309–319PubMed Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Luthy R, Nguyen HQ, Wooden S, Bennett L, Boone T, Shimamoto G, DeRose M, Elliott R, Colombero A, Tan HL, Trail G, Sullivan J, Davy E, Bucay N, Renshaw-Gegg L, Hughes TM, Hill D, Pattison W, Campbell P, Boyle WJ et al (1997) Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 89:309–319PubMed
135.
Zurück zum Zitat Atkins GJ, Haynes DR, Graves SE, Evdokiou A, Hay S, Bouralexis S, Findlay DM (2000) Expression of osteoclast differentiation signals by stromal elements of giant cell tumors. J Bone Miner Res 15:640–649PubMed Atkins GJ, Haynes DR, Graves SE, Evdokiou A, Hay S, Bouralexis S, Findlay DM (2000) Expression of osteoclast differentiation signals by stromal elements of giant cell tumors. J Bone Miner Res 15:640–649PubMed
136.
Zurück zum Zitat Brown JM, Corey E, Lee ZD, True LD, Yun TJ, Tondravi M, Vessella RL (2001) Osteoprotegerin and rank ligand expression in prostate cancer. Urology 57:611–616PubMed Brown JM, Corey E, Lee ZD, True LD, Yun TJ, Tondravi M, Vessella RL (2001) Osteoprotegerin and rank ligand expression in prostate cancer. Urology 57:611–616PubMed
137.
Zurück zum Zitat Chen G, Sircar K, Aprikian A, Potti A, Goltzman D, Rabbani SA (2006) Expression of RANKL/RANK/OPG in primary and metastatic human prostate cancer as markers of disease stage and functional regulation. Cancer 107:289–298PubMed Chen G, Sircar K, Aprikian A, Potti A, Goltzman D, Rabbani SA (2006) Expression of RANKL/RANK/OPG in primary and metastatic human prostate cancer as markers of disease stage and functional regulation. Cancer 107:289–298PubMed
138.
Zurück zum Zitat Perez-Martinez FC, Alonso V, Sarasa JL, Manzarbeitia F, Vela-Navarrete R, Calahorra FJ, Esbrit P (2008) Receptor activator of nuclear factor-kappaB ligand (RANKL) as a novel prognostic marker in prostate carcinoma. Histol Histopathol 23:709–715PubMed Perez-Martinez FC, Alonso V, Sarasa JL, Manzarbeitia F, Vela-Navarrete R, Calahorra FJ, Esbrit P (2008) Receptor activator of nuclear factor-kappaB ligand (RANKL) as a novel prognostic marker in prostate carcinoma. Histol Histopathol 23:709–715PubMed
139.
Zurück zum Zitat Zhang J, Dai J, Qi Y, Lin DL, Smith P, Strayhorn C, Mizokami A, Fu Z, Westman J, Keller ET (2001) Osteoprotegerin inhibits prostate cancer-induced osteoclastogenesis and prevents prostate tumor growth in the bone. J Clin Invest 107:1235–1244PubMed Zhang J, Dai J, Qi Y, Lin DL, Smith P, Strayhorn C, Mizokami A, Fu Z, Westman J, Keller ET (2001) Osteoprotegerin inhibits prostate cancer-induced osteoclastogenesis and prevents prostate tumor growth in the bone. J Clin Invest 107:1235–1244PubMed
140.
Zurück zum Zitat Morrissey C, Kostenuik PL, Brown LG, Vessella RL, Corey E (2007) Host-derived RANKL is responsible for osteolysis in a C4-2 human prostate cancer xenograft model of experimental bone metastases. BMC Cancer 7:148PubMed Morrissey C, Kostenuik PL, Brown LG, Vessella RL, Corey E (2007) Host-derived RANKL is responsible for osteolysis in a C4-2 human prostate cancer xenograft model of experimental bone metastases. BMC Cancer 7:148PubMed
141.
Zurück zum Zitat Zhang J, Dai J, Yao Z, Lu Y, Dougall W, Keller ET (2003) Soluble receptor activator of nuclear factor kappaB Fc diminishes prostate cancer progression in bone. Cancer Res 63:7883–7890PubMed Zhang J, Dai J, Yao Z, Lu Y, Dougall W, Keller ET (2003) Soluble receptor activator of nuclear factor kappaB Fc diminishes prostate cancer progression in bone. Cancer Res 63:7883–7890PubMed
142.
Zurück zum Zitat Luger NM, Honore P, Sabino MA, Schwei MJ, Rogers SD, Mach DB, Clohisy DR, Mantyh PW (2001) Osteoprotegerin diminishes advanced bone cancer pain. Cancer Res 61:4038–4047PubMed Luger NM, Honore P, Sabino MA, Schwei MJ, Rogers SD, Mach DB, Clohisy DR, Mantyh PW (2001) Osteoprotegerin diminishes advanced bone cancer pain. Cancer Res 61:4038–4047PubMed
143.
Zurück zum Zitat Honore P, Luger NM, Sabino MA, Schwei MJ, Rogers SD, Mach DB, O’Keefe PF, Ramnaraine ML, Clohisy DR, Mantyh PW (2000) Osteoprotegerin blocks bone cancer-induced skeletal destruction, skeletal pain and pain-related neurochemical reorganization of the spinal cord. Nat Med 6:521–528PubMed Honore P, Luger NM, Sabino MA, Schwei MJ, Rogers SD, Mach DB, O’Keefe PF, Ramnaraine ML, Clohisy DR, Mantyh PW (2000) Osteoprotegerin blocks bone cancer-induced skeletal destruction, skeletal pain and pain-related neurochemical reorganization of the spinal cord. Nat Med 6:521–528PubMed
144.
Zurück zum Zitat Armstrong AP, Miller RE, Jones JC, Zhang J, Keller ET, Dougall WC (2008) RANKL acts directly on RANK-expressing prostate tumor cells and mediates migration and expression of tumor metastasis genes. Prostate 68:92–104PubMed Armstrong AP, Miller RE, Jones JC, Zhang J, Keller ET, Dougall WC (2008) RANKL acts directly on RANK-expressing prostate tumor cells and mediates migration and expression of tumor metastasis genes. Prostate 68:92–104PubMed
145.
Zurück zum Zitat Holen I, Croucher PI, Hamdy FC, Eaton CL (2002) Osteoprotegerin (OPG) is a survival factor for human prostate cancer cells. Cancer Res 62:1619–1623PubMed Holen I, Croucher PI, Hamdy FC, Eaton CL (2002) Osteoprotegerin (OPG) is a survival factor for human prostate cancer cells. Cancer Res 62:1619–1623PubMed
146.
Zurück zum Zitat Fizazi K, Lipton A, Mariette X, Body JJ, Rahim Y, Gralow JR, Gao G, Wu L, Sohn W, Jun S (2009) Randomized phase II trial of denosumab in patients with bone metastases from prostate cancer, breast cancer, or other neoplasms after intravenous bisphosphonates. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 27:1564–1571 Fizazi K, Lipton A, Mariette X, Body JJ, Rahim Y, Gralow JR, Gao G, Wu L, Sohn W, Jun S (2009) Randomized phase II trial of denosumab in patients with bone metastases from prostate cancer, breast cancer, or other neoplasms after intravenous bisphosphonates. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 27:1564–1571
147.
Zurück zum Zitat Muir VJ, Scott LJ (2010) Denosumab: in cancer treatment-induced bone loss. BioDrugs 24:379–386PubMed Muir VJ, Scott LJ (2010) Denosumab: in cancer treatment-induced bone loss. BioDrugs 24:379–386PubMed
148.
Zurück zum Zitat Smith MR, Egerdie B, Hernandez Toriz N, Feldman R, Tammela TL, Saad F, Heracek J, Szwedowski M, Ke C, Kupic A, Leder BZ, Goessl C (2009) Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N Engl J Med 361:745–755PubMed Smith MR, Egerdie B, Hernandez Toriz N, Feldman R, Tammela TL, Saad F, Heracek J, Szwedowski M, Ke C, Kupic A, Leder BZ, Goessl C (2009) Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N Engl J Med 361:745–755PubMed
149.
Zurück zum Zitat Fizazi K, Carducci M, Smith M, Damiao R, Brown J, Karsh L, Milecki P, Shore N, Rader M, Wang H, Jiang Q, Tadros S, Dansey R, Goessl C (2011) Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet 377:813–822PubMed Fizazi K, Carducci M, Smith M, Damiao R, Brown J, Karsh L, Milecki P, Shore N, Rader M, Wang H, Jiang Q, Tadros S, Dansey R, Goessl C (2011) Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet 377:813–822PubMed
150.
Zurück zum Zitat Kim J, Lahl K, Hori S, Loddenkemper C, Chaudhry A, deRoos P, Rudensky A, Sparwasser T (2009) Cutting edge: depletion of Foxp3+ cells leads to induction of autoimmunity by specific ablation of regulatory T cells in genetically targeted mice. J Immunol 183:7631–7634PubMed Kim J, Lahl K, Hori S, Loddenkemper C, Chaudhry A, deRoos P, Rudensky A, Sparwasser T (2009) Cutting edge: depletion of Foxp3+ cells leads to induction of autoimmunity by specific ablation of regulatory T cells in genetically targeted mice. J Immunol 183:7631–7634PubMed
151.
Zurück zum Zitat Roato I, D’Amelio P, Gorassini E, Grimaldi A, Bonello L, Fiori C, Delsedime L, Tizzani A, De Libero A, Isaia G, Ferracini R (2008) Osteoclasts are active in bone forming metastases of prostate cancer patients. PloS one 3:e3627PubMed Roato I, D’Amelio P, Gorassini E, Grimaldi A, Bonello L, Fiori C, Delsedime L, Tizzani A, De Libero A, Isaia G, Ferracini R (2008) Osteoclasts are active in bone forming metastases of prostate cancer patients. PloS one 3:e3627PubMed
152.
Zurück zum Zitat Bruni-Cardoso A, Johnson LC, Vessella RL, Peterson TE, Lynch CC (2010) Osteoclast-derived matrix metalloproteinase-9 directly affects angiogenesis in the prostate tumor-bone microenvironment. Molecular cancer research: MCR 8:459–470PubMed Bruni-Cardoso A, Johnson LC, Vessella RL, Peterson TE, Lynch CC (2010) Osteoclast-derived matrix metalloproteinase-9 directly affects angiogenesis in the prostate tumor-bone microenvironment. Molecular cancer research: MCR 8:459–470PubMed
153.
Zurück zum Zitat Juarez P, Guise TA (2010) Tgf-Beta pathway as a therapeutic target in bone metastases. Curr Pharm Des 16:1301–1312PubMed Juarez P, Guise TA (2010) Tgf-Beta pathway as a therapeutic target in bone metastases. Curr Pharm Des 16:1301–1312PubMed
154.
Zurück zum Zitat Tomas D, Spajic B, Milosevic M, Demirovic A, Marusic Z, Kruslin B (2010) Intensity of stromal changes predicts biochemical recurrence-free survival in prostatic carcinoma. Scand J Urol Nephrol 44:284–290PubMed Tomas D, Spajic B, Milosevic M, Demirovic A, Marusic Z, Kruslin B (2010) Intensity of stromal changes predicts biochemical recurrence-free survival in prostatic carcinoma. Scand J Urol Nephrol 44:284–290PubMed
155.
Zurück zum Zitat Wang J, Ying G, Jung Y, Lu J, Zhu J, Pienta KJ, Taichman RS (2010) Characterization of phosphoglycerate kinase-1 expression of stromal cells derived from tumor microenvironment in prostate cancer progression. Cancer Res 70:471–480PubMed Wang J, Ying G, Jung Y, Lu J, Zhu J, Pienta KJ, Taichman RS (2010) Characterization of phosphoglycerate kinase-1 expression of stromal cells derived from tumor microenvironment in prostate cancer progression. Cancer Res 70:471–480PubMed
156.
Zurück zum Zitat Dai J, Hall CL, Escara-Wilke J, Mizokami A, Keller JM, Keller ET (2008) Prostate cancer induces bone metastasis through Wnt-induced bone morphogenetic protein-dependent and independent mechanisms. Cancer Res 68:5785–5794PubMed Dai J, Hall CL, Escara-Wilke J, Mizokami A, Keller JM, Keller ET (2008) Prostate cancer induces bone metastasis through Wnt-induced bone morphogenetic protein-dependent and independent mechanisms. Cancer Res 68:5785–5794PubMed
157.
Zurück zum Zitat Yang F, Tuxhorn JA, Ressler SJ, McAlhany SJ, Dang TD, Rowley DR (2005) Stromal expression of connective tissue growth factor promotes angiogenesis and prostate cancer tumorigenesis. Cancer Res 65:8887–8895PubMed Yang F, Tuxhorn JA, Ressler SJ, McAlhany SJ, Dang TD, Rowley DR (2005) Stromal expression of connective tissue growth factor promotes angiogenesis and prostate cancer tumorigenesis. Cancer Res 65:8887–8895PubMed
158.
Zurück zum Zitat Pinzone JJ, Hall BM, Thudi NK, Vonau M, Qiang YW, Rosol TJ, Shaughnessy JD Jr (2009) The role of Dickkopf-1 in bone development, homeostasis, and disease. Blood 113:517–525PubMed Pinzone JJ, Hall BM, Thudi NK, Vonau M, Qiang YW, Rosol TJ, Shaughnessy JD Jr (2009) The role of Dickkopf-1 in bone development, homeostasis, and disease. Blood 113:517–525PubMed
159.
Zurück zum Zitat Bagnato A, Loizidou M, Pflug BR, Curwen J, Growcott J (2011) Role of the endothelin axis and its antagonists in the treatment of cancer. Br J Pharmacol 163:220–233PubMed Bagnato A, Loizidou M, Pflug BR, Curwen J, Growcott J (2011) Role of the endothelin axis and its antagonists in the treatment of cancer. Br J Pharmacol 163:220–233PubMed
160.
Zurück zum Zitat Lin Y, Wang F (2010) FGF signalling in prostate development, tissue homoeostasis and tumorigenesis. Biosci Rep 30:285–291PubMed Lin Y, Wang F (2010) FGF signalling in prostate development, tissue homoeostasis and tumorigenesis. Biosci Rep 30:285–291PubMed
161.
Zurück zum Zitat Hurle RA, Davies G, Parr C, Mason MD, Jenkins SA, Kynaston HG, Jiang WG (2005) Hepatocyte growth factor/scatter factor and prostate cancer: a review. Histol Histopathol 20:1339–1349PubMed Hurle RA, Davies G, Parr C, Mason MD, Jenkins SA, Kynaston HG, Jiang WG (2005) Hepatocyte growth factor/scatter factor and prostate cancer: a review. Histol Histopathol 20:1339–1349PubMed
162.
Zurück zum Zitat Tawara K, Oxford JT, Jorcyk CL (2011) Clinical significance of interleukin (IL)-6 in cancer metastasis to bone: potential of anti-IL-6 therapies. Cancer Manag Res 3:177–189PubMed Tawara K, Oxford JT, Jorcyk CL (2011) Clinical significance of interleukin (IL)-6 in cancer metastasis to bone: potential of anti-IL-6 therapies. Cancer Manag Res 3:177–189PubMed
163.
Zurück zum Zitat Katiyar SK (2006) Matrix metalloproteinases in cancer metastasis: molecular targets for prostate cancer prevention by green tea polyphenols and grape seed proanthocyanidins. Endocr Metab Immune Disord Drug Targets 6:17–24PubMed Katiyar SK (2006) Matrix metalloproteinases in cancer metastasis: molecular targets for prostate cancer prevention by green tea polyphenols and grape seed proanthocyanidins. Endocr Metab Immune Disord Drug Targets 6:17–24PubMed
164.
Zurück zum Zitat Fili S, Karalaki M, Schaller B (2009) Mechanism of bone metastasis: the role of osteoprotegerin and of the host-tissue microenvironment-related survival factors. Cancer Lett 283:10–19PubMed Fili S, Karalaki M, Schaller B (2009) Mechanism of bone metastasis: the role of osteoprotegerin and of the host-tissue microenvironment-related survival factors. Cancer Lett 283:10–19PubMed
165.
Zurück zum Zitat Zhang X, Wang W, True LD, Vessella RL, Takayama TK (2009) Protease-activated receptor-1 is upregulated in reactive stroma of primary prostate cancer and bone metastasis. Prostate 69:727–736PubMed Zhang X, Wang W, True LD, Vessella RL, Takayama TK (2009) Protease-activated receptor-1 is upregulated in reactive stroma of primary prostate cancer and bone metastasis. Prostate 69:727–736PubMed
166.
Zurück zum Zitat Liao J, McCauley LK (2006) Skeletal metastasis: established and emerging roles of parathyroid hormone related protein (PTHrP). Cancer Metastasis Rev 25:559–571PubMed Liao J, McCauley LK (2006) Skeletal metastasis: established and emerging roles of parathyroid hormone related protein (PTHrP). Cancer Metastasis Rev 25:559–571PubMed
167.
Zurück zum Zitat Castellano D, Sepulveda JM, Garcia-Escobar I, Rodriguez-Antolin A, Sundlov A, Cortes-Funes H (2011) The role of RANK-ligand inhibition in cancer: the story of denosumab. Oncologist 16:136–145PubMed Castellano D, Sepulveda JM, Garcia-Escobar I, Rodriguez-Antolin A, Sundlov A, Cortes-Funes H (2011) The role of RANK-ligand inhibition in cancer: the story of denosumab. Oncologist 16:136–145PubMed
168.
Zurück zum Zitat Hirbe AC, Morgan EA, Weilbaecher KN (2010) The CXCR4/SDF-1 chemokine axis: a potential therapeutic target for bone metastases? Curr Pharm Des 16:1284–1290PubMed Hirbe AC, Morgan EA, Weilbaecher KN (2010) The CXCR4/SDF-1 chemokine axis: a potential therapeutic target for bone metastases? Curr Pharm Des 16:1284–1290PubMed
169.
Zurück zum Zitat Jones E, Pu H, Kyprianou N (2009) Targeting TGF-beta in prostate cancer: therapeutic possibilities during tumor progression. Expert Opin Ther Targets 13:227–234PubMed Jones E, Pu H, Kyprianou N (2009) Targeting TGF-beta in prostate cancer: therapeutic possibilities during tumor progression. Expert Opin Ther Targets 13:227–234PubMed
170.
Zurück zum Zitat Li Y, Cozzi PJ (2007) Targeting uPA/uPAR in prostate cancer. Cancer Treat Rev 33:521–527PubMed Li Y, Cozzi PJ (2007) Targeting uPA/uPAR in prostate cancer. Cancer Treat Rev 33:521–527PubMed
171.
Zurück zum Zitat Botelho F, Pina F, Lunet N (2010) VEGF and prostatic cancer: a systematic review. Eur J Cancer Prev 19:385–392PubMed Botelho F, Pina F, Lunet N (2010) VEGF and prostatic cancer: a systematic review. Eur J Cancer Prev 19:385–392PubMed
172.
Zurück zum Zitat Robinson DR, Zylstra CR, Williams BO (2008) Wnt signaling and prostate cancer. Curr Drug Targets 9:571–580PubMed Robinson DR, Zylstra CR, Williams BO (2008) Wnt signaling and prostate cancer. Curr Drug Targets 9:571–580PubMed
Metadaten
Titel
The PCa Tumor Microenvironment
verfasst von
Joseph L. Sottnik
Jian Zhang
Jill A. Macoska
Evan T. Keller
Publikationsdatum
01.12.2011
Verlag
Springer Netherlands
Erschienen in
Cancer Microenvironment / Ausgabe 3/2011
Print ISSN: 1875-2292
Elektronische ISSN: 1875-2284
DOI
https://doi.org/10.1007/s12307-011-0073-8

Weitere Artikel der Ausgabe 3/2011

Cancer Microenvironment 3/2011 Zur Ausgabe

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

25.04.2024 NSCLC Nachrichten

Das Risiko für Rezidiv oder Tod von Patienten und Patientinnen mit reseziertem ALK-positivem NSCLC ist unter einer adjuvanten Therapie mit dem Tyrosinkinase-Inhibitor Alectinib signifikant geringer als unter platinbasierter Chemotherapie.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.