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Erschienen in: Calcified Tissue International 1/2014

01.01.2014 | Review

Signaling Between Tumor Cells and the Host Bone Marrow Microenvironment

verfasst von: Natasa Kovacic, Peter I. Croucher, Michelle M. McDonald

Erschienen in: Calcified Tissue International | Ausgabe 1/2014

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Abstract

Tumor cells with high skeletal homing affinity express numerous cell surface receptors that bind ligands produced in bone. Upon arrival, these cells survive in the host environment, encompassed in close proximity to bone marrow cells. Interactions between tumor cells and cells of the host microenvironment are essential to not only tumor cell survival but also their activation and proliferation into environment-modifying tumors. Through the production of RANKL, PTHrP, cytokines, and integrins, activated tumor cells stimulate osteoclastogenesis, enhance bone resorption, and subsequently release matrix-bound proteins that further promote tumor growth and bone resorption. In addition, alterations in the TGF-β/BMP and Wnt signaling pathways via tumor cell growth can either stimulate or suppress osteoblastic bone formation and function, leading to sclerotic or lytic bone disease, respectively. Hence, the presence of tumor cells in bone dysregulates bone remodeling, dramatically impairing skeletal integrity. Furthermore, through complex mechanisms, cells of the immune system interact with tumor cells to further impact bone remodeling. Lastly, with alterations in bone cell activity, the environment is permissive to promoting tumor growth further, suggesting an interdependence between tumor cells and bone cells in metastatic bone disease and multiple myeloma.
Literatur
1.
Zurück zum Zitat Coleman RE (2006) Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res 12:6243s–6249sPubMed Coleman RE (2006) Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res 12:6243s–6249sPubMed
2.
Zurück zum Zitat Townson JL, Chambers AF (2006) Dormancy of solitary metastatic cells. Cell Cycle 5:1744–1750PubMed Townson JL, Chambers AF (2006) Dormancy of solitary metastatic cells. Cell Cycle 5:1744–1750PubMed
3.
Zurück zum Zitat Sun YX, Wang J, Shelburne CE, Lopatin DE, Chinnaiyan AM, Rubin MA, Pienta KJ, Taichman RS (2003) Expression of CXCR4 and CXCL12 (SDF-1) in human prostate cancers (PCa) in vivo. J Cell Biochem 89:462–473PubMed Sun YX, Wang J, Shelburne CE, Lopatin DE, Chinnaiyan AM, Rubin MA, Pienta KJ, Taichman RS (2003) Expression of CXCR4 and CXCL12 (SDF-1) in human prostate cancers (PCa) in vivo. J Cell Biochem 89:462–473PubMed
4.
Zurück zum Zitat Arya M, Patel HR, McGurk C, Tatoud R, Klocker H, Masters J, Williamson M (2004) The importance of the CXCL12-CXCR4 chemokine ligand–receptor interaction in prostate cancer metastasis. J Exp Ther Oncol 4:291–303PubMed Arya M, Patel HR, McGurk C, Tatoud R, Klocker H, Masters J, Williamson M (2004) The importance of the CXCL12-CXCR4 chemokine ligand–receptor interaction in prostate cancer metastasis. J Exp Ther Oncol 4:291–303PubMed
5.
Zurück zum Zitat Sun YX, Schneider A, Jung Y, Wang J, Dai J, Wang 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, Wang 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
6.
Zurück zum Zitat Wang J, Shiozawa Y, Wang J, Wang Y, Jung Y, Pienta KJ, Mehra R, Loberg R, Taichman RS (2008) The role of CXCR7/RDC1 as a chemokine receptor for CXCL12/SDF-1 in prostate cancer. J Biol Chem 283:4283–4294PubMed Wang J, Shiozawa Y, Wang J, Wang Y, Jung Y, Pienta KJ, Mehra R, Loberg R, Taichman RS (2008) The role of CXCR7/RDC1 as a chemokine receptor for CXCL12/SDF-1 in prostate cancer. J Biol Chem 283:4283–4294PubMed
7.
Zurück zum Zitat Kang H, Watkins G, Parr C, Douglas-Jones A, Mansel RE, Jiang WG (2005) Stromal cell derived factor-1: its influence on invasiveness and migration of breast cancer cells in vitro, and its association with prognosis and survival in human breast cancer. Breast Cancer Res 7:R402–R410PubMedCentralPubMed Kang H, Watkins G, Parr C, Douglas-Jones A, Mansel RE, Jiang WG (2005) Stromal cell derived factor-1: its influence on invasiveness and migration of breast cancer cells in vitro, and its association with prognosis and survival in human breast cancer. Breast Cancer Res 7:R402–R410PubMedCentralPubMed
8.
Zurück zum Zitat Kang Y, Siegel PM, Shu W, Drobnjak M, Kakonen SM, Cordon-Cardo C, Guise TA, Massague J (2003) A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 3:537–549PubMed Kang Y, Siegel PM, Shu W, Drobnjak M, Kakonen SM, Cordon-Cardo C, Guise TA, Massague J (2003) A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 3:537–549PubMed
9.
Zurück zum Zitat Muller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, McClanahan T, Murphy E, Yuan W, Wagner SN, Barrera JL, Mohar A, Verastegui E, Zlotnik A (2001) Involvement of chemokine receptors in breast cancer metastasis. Nature 410:50–56PubMed Muller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, McClanahan T, Murphy E, Yuan W, Wagner SN, Barrera JL, Mohar A, Verastegui E, Zlotnik A (2001) Involvement of chemokine receptors in breast cancer metastasis. Nature 410:50–56PubMed
10.
Zurück zum Zitat Vande Broek I, Leleu X, Schots R, Facon T, Vanderkerken K, Van Camp B, Van Riet I (2006) Clinical significance of chemokine receptor (CCR1, CCR2 and CXCR4) expression in human myeloma cells: the association with disease activity and survival. Haematologica 91:200–206PubMed Vande Broek I, Leleu X, Schots R, Facon T, Vanderkerken K, Van Camp B, Van Riet I (2006) Clinical significance of chemokine receptor (CCR1, CCR2 and CXCR4) expression in human myeloma cells: the association with disease activity and survival. Haematologica 91:200–206PubMed
11.
Zurück zum Zitat Zannettino AC, Farrugia AN, Kortesidis A, Manavis J, To LB, Martin SK, Diamond P, Tamamura H, Lapidot T, Fujii N, Gronthos S (2005) Elevated serum levels of stromal-derived factor-1alpha are associated with increased osteoclast activity and osteolytic bone disease in multiple myeloma patients. Cancer Res 65:1700–1709PubMed Zannettino AC, Farrugia AN, Kortesidis A, Manavis J, To LB, Martin SK, Diamond P, Tamamura H, Lapidot T, Fujii N, Gronthos S (2005) Elevated serum levels of stromal-derived factor-1alpha are associated with increased osteoclast activity and osteolytic bone disease in multiple myeloma patients. Cancer Res 65:1700–1709PubMed
12.
Zurück zum Zitat Menu E, De Leenheer E, De Raeve H, Coulton L, Imanishi T, Miyashita K, Van Valckenborgh E, Van Riet I, Van Camp B, Horuk R, Croucher P, Vanderkerken K (2006) Role of CCR1 and CCR5 in homing and growth of multiple myeloma and in the development of osteolytic lesions: a study in the 5TMM model. Clin Exp Metastasis 23:291–300PubMed Menu E, De Leenheer E, De Raeve H, Coulton L, Imanishi T, Miyashita K, Van Valckenborgh E, Van Riet I, Van Camp B, Horuk R, Croucher P, Vanderkerken K (2006) Role of CCR1 and CCR5 in homing and growth of multiple myeloma and in the development of osteolytic lesions: a study in the 5TMM model. Clin Exp Metastasis 23:291–300PubMed
13.
Zurück zum Zitat Jung Y, Wang J, Song J, Shiozawa Y, Wang J, Havens A, Wang Z, Sun YX, Emerson SG, Krebsbach PH, Taichman RS (2007) Annexin II expressed by osteoblasts and endothelial cells regulates stem cell adhesion, homing, and engraftment following transplantation. Blood 110:82–90PubMed Jung Y, Wang J, Song J, Shiozawa Y, Wang J, Havens A, Wang Z, Sun YX, Emerson SG, Krebsbach PH, Taichman RS (2007) Annexin II expressed by osteoblasts and endothelial cells regulates stem cell adhesion, homing, and engraftment following transplantation. Blood 110:82–90PubMed
14.
Zurück zum Zitat Shiozawa Y, Havens AM, Jung Y, Ziegler AM, Pedersen EA, Wang J, Wang J, Lu G, Roodman GD, Loberg RD, Pienta KJ, Taichman RS (2008) Annexin II/annexin II receptor axis regulates adhesion, migration, homing, and growth of prostate cancer. J Cell Biochem 105:370–380PubMedCentralPubMed Shiozawa Y, Havens AM, Jung Y, Ziegler AM, Pedersen EA, Wang J, Wang J, Lu G, Roodman GD, Loberg RD, Pienta KJ, Taichman RS (2008) Annexin II/annexin II receptor axis regulates adhesion, migration, homing, and growth of prostate cancer. J Cell Biochem 105:370–380PubMedCentralPubMed
15.
Zurück zum Zitat Tamura D, Hiraga T, Myoui A, Yoshikawa H, Yoneda T (2008) Cadherin-11-mediated interactions with bone marrow stromal/osteoblastic cells support selective colonization of breast cancer cells in bone. Int J Oncol 33:17–24PubMed Tamura D, Hiraga T, Myoui A, Yoshikawa H, Yoneda T (2008) Cadherin-11-mediated interactions with bone marrow stromal/osteoblastic cells support selective colonization of breast cancer cells in bone. Int J Oncol 33:17–24PubMed
16.
Zurück zum Zitat Lee YC, Bilen MA, Yu G, Lin SC, Huang CF, Ortiz A, Cho H, Song JH, Satcher RL, Kuang J, Gallick GE, Yu-Lee LY, Huang W, Lin SH (2013) Inhibition of cell adhesion by an anti-cadherin 11 antibody prevents bone metastasis. Mol Cancer Res 29(8):430–435 Lee YC, Bilen MA, Yu G, Lin SC, Huang CF, Ortiz A, Cho H, Song JH, Satcher RL, Kuang J, Gallick GE, Yu-Lee LY, Huang W, Lin SH (2013) Inhibition of cell adhesion by an anti-cadherin 11 antibody prevents bone metastasis. Mol Cancer Res 29(8):430–435
17.
Zurück zum Zitat Rudland PS, Platt-Higgins A, El-Tanani M, De Silva Rudland S, Barraclough R, Winstanley JH, Howitt R, West CR (2002) Prognostic significance of the metastasis-associated protein osteopontin in human breast cancer. Cancer Res 62:3417–3427PubMed Rudland PS, Platt-Higgins A, El-Tanani M, De Silva Rudland S, Barraclough R, Winstanley JH, Howitt R, West CR (2002) Prognostic significance of the metastasis-associated protein osteopontin in human breast cancer. Cancer Res 62:3417–3427PubMed
18.
Zurück zum Zitat Thalmann GN, Sikes RA, Devoll RE, Kiefer JA, Markwalder R, Klima I, Farach-Carson CM, Studer UE, Chung LW (1999) Osteopontin: possible role in prostate cancer progression. Clin Cancer Res 5:2271–2277PubMed Thalmann GN, Sikes RA, Devoll RE, Kiefer JA, Markwalder R, Klima I, Farach-Carson CM, Studer UE, Chung LW (1999) Osteopontin: possible role in prostate cancer progression. Clin Cancer Res 5:2271–2277PubMed
19.
Zurück zum Zitat Nilsson SK, Johnston HM, Whitty GA, Williams B, Webb RJ, Denhardt DT, Bertoncello I, Bendall LJ, Simmons PJ, Haylock DN (2005) Osteopontin, a key component of the hematopoietic stem cell niche and regulator of primitive hematopoietic progenitor cells. Blood 106:1232–1239PubMed Nilsson SK, Johnston HM, Whitty GA, Williams B, Webb RJ, Denhardt DT, Bertoncello I, Bendall LJ, Simmons PJ, Haylock DN (2005) Osteopontin, a key component of the hematopoietic stem cell niche and regulator of primitive hematopoietic progenitor cells. Blood 106:1232–1239PubMed
20.
Zurück zum Zitat Joseph J, Shiozawa Y, Jung Y, Kim JK, Pedersen E, Mishra A, Zalucha JL, Wang J, Keller ET, Pienta KJ, Taichman RS (2012) Disseminated prostate cancer cells can instruct hematopoietic stem and progenitor cells to regulate bone phenotype. Mol Cancer Res 10:282–292PubMedCentralPubMed Joseph J, Shiozawa Y, Jung Y, Kim JK, Pedersen E, Mishra A, Zalucha JL, Wang J, Keller ET, Pienta KJ, Taichman RS (2012) Disseminated prostate cancer cells can instruct hematopoietic stem and progenitor cells to regulate bone phenotype. Mol Cancer Res 10:282–292PubMedCentralPubMed
21.
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 121:1298–1312PubMedCentralPubMed 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 121:1298–1312PubMedCentralPubMed
22.
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
23.
Zurück zum Zitat Li J, Sarosi I, Yan XQ, Morony S, Capparelli C, Tan HL, McCabe S, Elliott R, Scully S, Van G, Kaufman S, Juan SC, Sun Y, Tarpley J, Martin L, Christensen K, McCabe J, Kostenuik P, Hsu H, Fletcher F, Dunstan CR, Lacey DL, Boyle WJ (2000) RANK is the intrinsic hematopoietic cell surface receptor that controls osteoclastogenesis and regulation of bone mass and calcium metabolism. Proc Natl Acad Sci USA 97:1566–1571PubMed Li J, Sarosi I, Yan XQ, Morony S, Capparelli C, Tan HL, McCabe S, Elliott R, Scully S, Van G, Kaufman S, Juan SC, Sun Y, Tarpley J, Martin L, Christensen K, McCabe J, Kostenuik P, Hsu H, Fletcher F, Dunstan CR, Lacey DL, Boyle WJ (2000) RANK is the intrinsic hematopoietic cell surface receptor that controls osteoclastogenesis and regulation of bone mass and calcium metabolism. Proc Natl Acad Sci USA 97:1566–1571PubMed
24.
Zurück zum Zitat Ehrlich LA, Roodman GD (2005) The role of immune cells and inflammatory cytokines in Paget’s disease and multiple myeloma. Immunol Rev 208:252–266PubMed Ehrlich LA, Roodman GD (2005) The role of immune cells and inflammatory cytokines in Paget’s disease and multiple myeloma. Immunol Rev 208:252–266PubMed
25.
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, Sander S, Van G, Tarpley J, Derby P, Lee R, Boyle WJ (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, Sander S, Van G, Tarpley J, Derby P, Lee R, Boyle WJ (1997) Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 89:309–319PubMed
26.
Zurück zum Zitat Thomas RJ, Guise TA, Yin JJ, Elliott J, Horwood NJ, Martin TJ, Gillespie MT (1999) Breast cancer cells interact with osteoblasts to support osteoclast formation. Endocrinology 140:4451–4458PubMed Thomas RJ, Guise TA, Yin JJ, Elliott J, Horwood NJ, Martin TJ, Gillespie MT (1999) Breast cancer cells interact with osteoblasts to support osteoclast formation. Endocrinology 140:4451–4458PubMed
27.
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
28.
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 107:1235–1244PubMedCentralPubMed 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 107:1235–1244PubMedCentralPubMed
29.
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 7:148PubMedCentralPubMed 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 7:148PubMedCentralPubMed
30.
Zurück zum Zitat Croucher PI, Shipman CM, Lippitt J, Perry M, Asosingh K, Hijzen A, Brabbs AC, van Beek EJ, Holen I, Skerry TM, Dunstan CR, Russell GR, Van Camp B, Vanderkerken K (2001) Osteoprotegerin inhibits the development of osteolytic bone disease in multiple myeloma. Blood 98:3534–3540PubMed Croucher PI, Shipman CM, Lippitt J, Perry M, Asosingh K, Hijzen A, Brabbs AC, van Beek EJ, Holen I, Skerry TM, Dunstan CR, Russell GR, Van Camp B, Vanderkerken K (2001) Osteoprotegerin inhibits the development of osteolytic bone disease in multiple myeloma. Blood 98:3534–3540PubMed
31.
Zurück zum Zitat Farrugia AN, Atkins GJ, To LB, Pan B, Horvath N, Kostakis P, Findlay DM, Bardy P, Zannettino AC (2003) Receptor activator of nuclear factor-kappaB ligand expression by human myeloma cells mediates osteoclast formation in vitro and correlates with bone destruction in vivo. Cancer Res 63:5438–5445PubMed Farrugia AN, Atkins GJ, To LB, Pan B, Horvath N, Kostakis P, Findlay DM, Bardy P, Zannettino AC (2003) Receptor activator of nuclear factor-kappaB ligand expression by human myeloma cells mediates osteoclast formation in vitro and correlates with bone destruction in vivo. Cancer Res 63:5438–5445PubMed
32.
Zurück zum Zitat Sezer O, Heider U, Jakob C, Eucker J, Possinger K (2002) Human bone marrow myeloma cells express RANKL. J Clin Oncol 20:353–354PubMed Sezer O, Heider U, Jakob C, Eucker J, Possinger K (2002) Human bone marrow myeloma cells express RANKL. J Clin Oncol 20:353–354PubMed
33.
Zurück zum Zitat Pearse RN, Sordillo EM, Yaccoby S, Wong BR, Liau DF, Colman N, Michaeli J, Epstein J, Choi Y (2001) Multiple myeloma disrupts the TRANCE/osteoprotegerin cytokine axis to trigger bone destruction and promote tumor progression. Proc Natl Acad Sci USA 98:11581–11586PubMed Pearse RN, Sordillo EM, Yaccoby S, Wong BR, Liau DF, Colman N, Michaeli J, Epstein J, Choi Y (2001) Multiple myeloma disrupts the TRANCE/osteoprotegerin cytokine axis to trigger bone destruction and promote tumor progression. Proc Natl Acad Sci USA 98:11581–11586PubMed
34.
Zurück zum Zitat Giuliani N, Bataille R, Mancini C, Lazzaretti M, Barille S (2001) Myeloma cells induce imbalance in the osteoprotegerin/osteoprotegerin ligand system in the human bone marrow environment. Blood 98:3527–3533PubMed Giuliani N, Bataille R, Mancini C, Lazzaretti M, Barille S (2001) Myeloma cells induce imbalance in the osteoprotegerin/osteoprotegerin ligand system in the human bone marrow environment. Blood 98:3527–3533PubMed
35.
Zurück zum Zitat Shipman CM, Croucher PI (2003) Osteoprotegerin is a soluble decoy receptor for tumor necrosis factor-related apoptosis-inducing ligand/Apo2 ligand and can function as a paracrine survival factor for human myeloma cells. Cancer Res 63:912–916PubMed Shipman CM, Croucher PI (2003) Osteoprotegerin is a soluble decoy receptor for tumor necrosis factor-related apoptosis-inducing ligand/Apo2 ligand and can function as a paracrine survival factor for human myeloma cells. Cancer Res 63:912–916PubMed
36.
Zurück zum Zitat Heath DJ, Vanderkerken K, Cheng X, Gallagher O, Prideaux M, Murali R, Croucher PI (2007) An osteoprotegerin-like peptidomimetic inhibits osteoclastic bone resorption and osteolytic bone disease in myeloma. Cancer Res 67:202–208PubMed Heath DJ, Vanderkerken K, Cheng X, Gallagher O, Prideaux M, Murali R, Croucher PI (2007) An osteoprotegerin-like peptidomimetic inhibits osteoclastic bone resorption and osteolytic bone disease in myeloma. Cancer Res 67:202–208PubMed
37.
Zurück zum Zitat Yaccoby S, Wezeman MJ, Henderson A, Cottler-Fox M, Yi Q, Barlogie B, Epstein J (2004) Cancer and the microenvironment: myeloma–osteoclast interactions as a model. Cancer Res 64:2016–2023PubMed Yaccoby S, Wezeman MJ, Henderson A, Cottler-Fox M, Yi Q, Barlogie B, Epstein J (2004) Cancer and the microenvironment: myeloma–osteoclast interactions as a model. Cancer Res 64:2016–2023PubMed
38.
Zurück zum Zitat Canon JR, Roudier M, Bryant R, Morony S, Stolina M, Kostenuik PJ, Dougall WC (2008) Inhibition of RANKL blocks skeletal tumor progression and improves survival in a mouse model of breast cancer bone metastasis. Clin Exp Metastasis 25:119–129PubMed Canon JR, Roudier M, Bryant R, Morony S, Stolina M, Kostenuik PJ, Dougall WC (2008) Inhibition of RANKL blocks skeletal tumor progression and improves survival in a mouse model of breast cancer bone metastasis. Clin Exp Metastasis 25:119–129PubMed
39.
Zurück zum Zitat Holland PM, Miller R, Jones J, Douangpanya H, Piasecki J, Roudier M, Dougall WC (2010) Combined therapy with the RANKL inhibitor RANK-Fc and rhApo2L/TRAIL/dulanermin reduces bone lesions and skeletal tumor burden in a model of breast cancer skeletal metastasis. Cancer Biol Ther 9:539–550PubMed Holland PM, Miller R, Jones J, Douangpanya H, Piasecki J, Roudier M, Dougall WC (2010) Combined therapy with the RANKL inhibitor RANK-Fc and rhApo2L/TRAIL/dulanermin reduces bone lesions and skeletal tumor burden in a model of breast cancer skeletal metastasis. Cancer Biol Ther 9:539–550PubMed
40.
Zurück zum Zitat Miller RE, Roudier M, Jones J, Armstrong A, Canon J, Dougall WC (2008) RANK ligand inhibition plus docetaxel improves survival and reduces tumor burden in a murine model of prostate cancer bone metastasis. Mol Cancer Ther 7:2160–2169PubMed Miller RE, Roudier M, Jones J, Armstrong A, Canon J, Dougall WC (2008) RANK ligand inhibition plus docetaxel improves survival and reduces tumor burden in a murine model of prostate cancer bone metastasis. Mol Cancer Ther 7:2160–2169PubMed
41.
Zurück zum Zitat Lipton A, Steger GG, Figueroa J, Alvarado C, Solal-Celigny P, Body JJ, de Boer R, Berardi R, Gascon P, Tonkin KS, Coleman R, Paterson AH, Peterson MC, Fan M, Kinsey A, Jun S (2007) Randomized active-controlled phase II study of denosumab efficacy and safety in patients with breast cancer–related bone metastases. J Clin Oncol 25:4431–4437PubMed Lipton A, Steger GG, Figueroa J, Alvarado C, Solal-Celigny P, Body JJ, de Boer R, Berardi R, Gascon P, Tonkin KS, Coleman R, Paterson AH, Peterson MC, Fan M, Kinsey A, Jun S (2007) Randomized active-controlled phase II study of denosumab efficacy and safety in patients with breast cancer–related bone metastases. J Clin Oncol 25:4431–4437PubMed
42.
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. J Clin Oncol 27:1564–1571PubMed 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. J Clin Oncol 27:1564–1571PubMed
43.
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
44.
Zurück zum Zitat Guise TA (1997) Parathyroid hormone–related protein and bone metastases. Cancer 80:1572–1580PubMed Guise TA (1997) Parathyroid hormone–related protein and bone metastases. Cancer 80:1572–1580PubMed
45.
Zurück zum Zitat Powell GJ, Southby J, Danks JA, Stillwell RG, Hayman JA, Henderson MA, Bennett RC, Martin TJ (1991) Localization of parathyroid hormone–related protein in breast cancer metastases: increased incidence in bone compared with other sites. Cancer Res 51:3059–3061PubMed Powell GJ, Southby J, Danks JA, Stillwell RG, Hayman JA, Henderson MA, Bennett RC, Martin TJ (1991) Localization of parathyroid hormone–related protein in breast cancer metastases: increased incidence in bone compared with other sites. Cancer Res 51:3059–3061PubMed
46.
Zurück zum Zitat Guise TA, Yin JJ, Taylor SD, Kumagai Y, Dallas M, Boyce BF, Yoneda T, Mundy GR (1996) Evidence for a causal role of parathyroid hormone–related protein in the pathogenesis of human breast cancer-mediated osteolysis. J Clin Invest 98:1544–1549PubMedCentralPubMed Guise TA, Yin JJ, Taylor SD, Kumagai Y, Dallas M, Boyce BF, Yoneda T, Mundy GR (1996) Evidence for a causal role of parathyroid hormone–related protein in the pathogenesis of human breast cancer-mediated osteolysis. J Clin Invest 98:1544–1549PubMedCentralPubMed
47.
Zurück zum Zitat Johnson RW, Nguyen MP, Padalecki SS, Grubbs BG, Merkel AR, Oyajobi BO, Matrisian LM, Mundy GR, Sterling JA (2011) TGF-beta promotion of Gli2-induced expression of parathyroid hormone-related protein, an important osteolytic factor in bone metastasis, is independent of canonical Hedgehog signaling. Cancer Res 71:822–831PubMedCentralPubMed Johnson RW, Nguyen MP, Padalecki SS, Grubbs BG, Merkel AR, Oyajobi BO, Matrisian LM, Mundy GR, Sterling JA (2011) TGF-beta promotion of Gli2-induced expression of parathyroid hormone-related protein, an important osteolytic factor in bone metastasis, is independent of canonical Hedgehog signaling. Cancer Res 71:822–831PubMedCentralPubMed
48.
Zurück zum Zitat Lee SK, Lorenzo JA (1999) Parathyroid hormone stimulates TRANCE and inhibits osteoprotegerin messenger ribonucleic acid expression in murine bone marrow cultures: correlation with osteoclast-like cell formation. Endocrinology 140:3552–3561PubMed Lee SK, Lorenzo JA (1999) Parathyroid hormone stimulates TRANCE and inhibits osteoprotegerin messenger ribonucleic acid expression in murine bone marrow cultures: correlation with osteoclast-like cell formation. Endocrinology 140:3552–3561PubMed
49.
Zurück zum Zitat Bryden AA, Hoyland JA, Freemont AJ, Clarke NW, George NJ (2002) Parathyroid hormone related peptide and receptor expression in paired primary prostate cancer and bone metastases. Br J Cancer 86:322–325PubMedCentralPubMed Bryden AA, Hoyland JA, Freemont AJ, Clarke NW, George NJ (2002) Parathyroid hormone related peptide and receptor expression in paired primary prostate cancer and bone metastases. Br J Cancer 86:322–325PubMedCentralPubMed
50.
Zurück zum Zitat Voorhees PM, Manges RF, Sonneveld P, Jagannath S, Somlo G, Krishnan A, Lentzsch S, Frank RC, Zweegman S, Wijermans PW, Orlowski RZ, Kranenburg B, Hall B, Casneuf T, Qin X, van de Velde H, Xie H, Thomas SK (2013) A phase 2 multicentre study of siltuximab, an anti-interleukin-6 monoclonal antibody, in patients with relapsed or refractory multiple myeloma. British J Haematol 161:357–366 Voorhees PM, Manges RF, Sonneveld P, Jagannath S, Somlo G, Krishnan A, Lentzsch S, Frank RC, Zweegman S, Wijermans PW, Orlowski RZ, Kranenburg B, Hall B, Casneuf T, Qin X, van de Velde H, Xie H, Thomas SK (2013) A phase 2 multicentre study of siltuximab, an anti-interleukin-6 monoclonal antibody, in patients with relapsed or refractory multiple myeloma. British J Haematol 161:357–366
51.
Zurück zum Zitat Adebanjo OA, Moonga BS, Yamate T, Sun L, Minkin C, Abe E, Zaidi M (1998) Mode of action of interleukin-6 on mature osteoclasts. Novel interactions with extracellular Ca2+ sensing in the regulation of osteoclastic bone resorption. J Cell Biol 142:1347–1356PubMed Adebanjo OA, Moonga BS, Yamate T, Sun L, Minkin C, Abe E, Zaidi M (1998) Mode of action of interleukin-6 on mature osteoclasts. Novel interactions with extracellular Ca2+ sensing in the regulation of osteoclastic bone resorption. J Cell Biol 142:1347–1356PubMed
52.
Zurück zum Zitat Palmqvist P, Persson E, Conaway HH, Lerner UH (2002) IL-6, leukemia inhibitory factor, and oncostatin M stimulate bone resorption and regulate the expression of receptor activator of NF-kappa B ligand, osteoprotegerin, and receptor activator of NF-kappaB in mouse calvariae. J Immunol 169:3353–3362PubMed Palmqvist P, Persson E, Conaway HH, Lerner UH (2002) IL-6, leukemia inhibitory factor, and oncostatin M stimulate bone resorption and regulate the expression of receptor activator of NF-kappa B ligand, osteoprotegerin, and receptor activator of NF-kappaB in mouse calvariae. J Immunol 169:3353–3362PubMed
53.
Zurück zum Zitat Hobisch A, Rogatsch H, Hittmair A, Fuchs D, Bartsch G Jr, Klocker H, Bartsch G, Culig Z (2000) Immunohistochemical localization of interleukin-6 and its receptor in benign, premalignant and malignant prostate tissue. J Pathol 191:239–244PubMed Hobisch A, Rogatsch H, Hittmair A, Fuchs D, Bartsch G Jr, Klocker H, Bartsch G, Culig Z (2000) Immunohistochemical localization of interleukin-6 and its receptor in benign, premalignant and malignant prostate tissue. J Pathol 191:239–244PubMed
54.
Zurück zum Zitat Siegall CB, Schwab G, Nordan RP, FitzGerald DJ, Pastan I (1990) Expression of the interleukin 6 receptor and interleukin 6 in prostate carcinoma cells. Cancer Res 50:7786–7788PubMed Siegall CB, Schwab G, Nordan RP, FitzGerald DJ, Pastan I (1990) Expression of the interleukin 6 receptor and interleukin 6 in prostate carcinoma cells. Cancer Res 50:7786–7788PubMed
55.
Zurück zum Zitat Knupfer H, Schmidt R, Stanitz D, Brauckhoff M, Schonfelder M, Preiss R (2004) CYP2C and IL-6 expression in breast cancer. Breast 13:28–34PubMed Knupfer H, Schmidt R, Stanitz D, Brauckhoff M, Schonfelder M, Preiss R (2004) CYP2C and IL-6 expression in breast cancer. Breast 13:28–34PubMed
56.
Zurück zum Zitat Kinder M, Chislock E, Bussard KM, Shuman L, Mastro AM (2008) Metastatic breast cancer induces an osteoblast inflammatory response. Exp Cell Res 314:173–183PubMed Kinder M, Chislock E, Bussard KM, Shuman L, Mastro AM (2008) Metastatic breast cancer induces an osteoblast inflammatory response. Exp Cell Res 314:173–183PubMed
57.
Zurück zum Zitat Sethi N, Dai X, Winter CG, Kang Y (2011) Tumor-derived JAGGED1 promotes osteolytic bone metastasis of breast cancer by engaging notch signaling in bone cells. Cancer Cell 19:192–205PubMedCentralPubMed Sethi N, Dai X, Winter CG, Kang Y (2011) Tumor-derived JAGGED1 promotes osteolytic bone metastasis of breast cancer by engaging notch signaling in bone cells. Cancer Cell 19:192–205PubMedCentralPubMed
58.
Zurück zum Zitat Giuliani N, Colla S, Sala R, Moroni M, Lazzaretti M, La Monica S, Bonomini S, Hojden M, Sammarelli G, Barille S, Bataille R, Rizzoli V (2002) Human myeloma cells stimulate the receptor activator of nuclear factor-kappa B ligand (RANKL) in T lymphocytes: a potential role in multiple myeloma bone disease. Blood 100:4615–4621PubMed Giuliani N, Colla S, Sala R, Moroni M, Lazzaretti M, La Monica S, Bonomini S, Hojden M, Sammarelli G, Barille S, Bataille R, Rizzoli V (2002) Human myeloma cells stimulate the receptor activator of nuclear factor-kappa B ligand (RANKL) in T lymphocytes: a potential role in multiple myeloma bone disease. Blood 100:4615–4621PubMed
59.
Zurück zum Zitat Giuliani N, Colla S, Morandi F, Lazzaretti M, Sala R, Bonomini S, Grano M, Colucci S, Svaldi M, Rizzoli V (2005) Myeloma cells block RUNX2/CBFA1 activity in human bone marrow osteoblast progenitors and inhibit osteoblast formation and differentiation. Blood 106:2472–2483PubMed Giuliani N, Colla S, Morandi F, Lazzaretti M, Sala R, Bonomini S, Grano M, Colucci S, Svaldi M, Rizzoli V (2005) Myeloma cells block RUNX2/CBFA1 activity in human bone marrow osteoblast progenitors and inhibit osteoblast formation and differentiation. Blood 106:2472–2483PubMed
60.
Zurück zum Zitat Bendre MS, Montague DC, Peery T, Akel NS, Gaddy D, Suva LJ (2003) Interleukin-8 stimulation of osteoclastogenesis and bone resorption is a mechanism for the increased osteolysis of metastatic bone disease. Bone 33:28–37PubMed Bendre MS, Montague DC, Peery T, Akel NS, Gaddy D, Suva LJ (2003) Interleukin-8 stimulation of osteoclastogenesis and bone resorption is a mechanism for the increased osteolysis of metastatic bone disease. Bone 33:28–37PubMed
61.
Zurück zum Zitat Markovina S, Callander NS, O’Connor SL, Xu G, Shi Y, Leith CP, Kim K, Trivedi P, Kim J, Hematti P, Miyamoto S (2010) Bone marrow stromal cells from multiple myeloma patients uniquely induce bortezomib resistant NF-kappaB activity in myeloma cells. Mol Cancer 9:176PubMedCentralPubMed Markovina S, Callander NS, O’Connor SL, Xu G, Shi Y, Leith CP, Kim K, Trivedi P, Kim J, Hematti P, Miyamoto S (2010) Bone marrow stromal cells from multiple myeloma patients uniquely induce bortezomib resistant NF-kappaB activity in myeloma cells. Mol Cancer 9:176PubMedCentralPubMed
62.
Zurück zum Zitat Wright LM, Maloney W, Yu X, Kindle L, Collin-Osdoby P, Osdoby P (2005) Stromal cell-derived factor-1 binding to its chemokine receptor CXCR4 on precursor cells promotes the chemotactic recruitment, development and survival of human osteoclasts. Bone 36:840–853PubMed Wright LM, Maloney W, Yu X, Kindle L, Collin-Osdoby P, Osdoby P (2005) Stromal cell-derived factor-1 binding to its chemokine receptor CXCR4 on precursor cells promotes the chemotactic recruitment, development and survival of human osteoclasts. Bone 36:840–853PubMed
63.
Zurück zum Zitat Han JH, Choi SJ, Kurihara N, Koide M, Oba Y, Roodman GD (2001) Macrophage inflammatory protein-1alpha is an osteoclastogenic factor in myeloma that is independent of receptor activator of nuclear factor kappaB ligand. Blood 97:3349–3353PubMed Han JH, Choi SJ, Kurihara N, Koide M, Oba Y, Roodman GD (2001) Macrophage inflammatory protein-1alpha is an osteoclastogenic factor in myeloma that is independent of receptor activator of nuclear factor kappaB ligand. Blood 97:3349–3353PubMed
64.
Zurück zum Zitat Abe M, Hiura K, Wilde J, Moriyama K, Hashimoto T, Ozaki S, Wakatsuki S, Kosaka M, Kido S, Inoue D, Matsumoto T (2002) Role for macrophage inflammatory protein (MIP)-1alpha and MIP-1beta in the development of osteolytic lesions in multiple myeloma. Blood 100:2195–2202PubMed Abe M, Hiura K, Wilde J, Moriyama K, Hashimoto T, Ozaki S, Wakatsuki S, Kosaka M, Kido S, Inoue D, Matsumoto T (2002) Role for macrophage inflammatory protein (MIP)-1alpha and MIP-1beta in the development of osteolytic lesions in multiple myeloma. Blood 100:2195–2202PubMed
65.
Zurück zum Zitat Oyajobi BO, Franchin G, Williams PJ, Pulkrabek D, Gupta A, Munoz S, Grubbs B, Zhao M, Chen D, Sherry B, Mundy GR (2003) Dual effects of macrophage inflammatory protein-1alpha on osteolysis and tumor burden in the murine 5TGM1 model of myeloma bone disease. Blood 102:311–319PubMed Oyajobi BO, Franchin G, Williams PJ, Pulkrabek D, Gupta A, Munoz S, Grubbs B, Zhao M, Chen D, Sherry B, Mundy GR (2003) Dual effects of macrophage inflammatory protein-1alpha on osteolysis and tumor burden in the murine 5TGM1 model of myeloma bone disease. Blood 102:311–319PubMed
66.
Zurück zum Zitat DuPre SA, Redelman D, Hunter KW Jr (2007) The mouse mammary carcinoma 4T1: characterization of the cellular landscape of primary tumors and metastatic tumor foci. Int J Exp Pathol 88:351–360PubMedCentralPubMed DuPre SA, Redelman D, Hunter KW Jr (2007) The mouse mammary carcinoma 4T1: characterization of the cellular landscape of primary tumors and metastatic tumor foci. Int J Exp Pathol 88:351–360PubMedCentralPubMed
67.
Zurück zum Zitat Duong LT, Lakkakorpi P, Nakamura I, Rodan GA (2000) Integrins and signaling in osteoclast function. Matrix Biol 19:97–105PubMed Duong LT, Lakkakorpi P, Nakamura I, Rodan GA (2000) Integrins and signaling in osteoclast function. Matrix Biol 19:97–105PubMed
68.
Zurück zum Zitat Lu X, Mu E, Wei Y, Riethdorf S, Yang Q, Yuan M, Yan J, Hua Y, Tiede BJ, Lu X, Haffty BG, Pantel K, Massague J, Kang Y (2011) VCAM-1 promotes osteolytic expansion of indolent bone micrometastasis of breast cancer by engaging alpha4beta1-positive osteoclast progenitors. Cancer Cell 20:701–714PubMedCentralPubMed Lu X, Mu E, Wei Y, Riethdorf S, Yang Q, Yuan M, Yan J, Hua Y, Tiede BJ, Lu X, Haffty BG, Pantel K, Massague J, Kang Y (2011) VCAM-1 promotes osteolytic expansion of indolent bone micrometastasis of breast cancer by engaging alpha4beta1-positive osteoclast progenitors. Cancer Cell 20:701–714PubMedCentralPubMed
69.
Zurück zum Zitat Nannuru KC, Futakuchi M, Varney ML, Vincent TM, Marcusson EG, Singh RK (2010) Matrix metalloproteinase (MMP)-13 regulates mammary tumor-induced osteolysis by activating MMP9 and transforming growth factor-beta signaling at the tumor–bone interface. Cancer Res 70:3494–3504PubMedCentralPubMed Nannuru KC, Futakuchi M, Varney ML, Vincent TM, Marcusson EG, Singh RK (2010) Matrix metalloproteinase (MMP)-13 regulates mammary tumor-induced osteolysis by activating MMP9 and transforming growth factor-beta signaling at the tumor–bone interface. Cancer Res 70:3494–3504PubMedCentralPubMed
70.
Zurück zum Zitat Bonfil RD, Dong Z, Trindade Filho JC, Sabbota A, Osenkowski P, Nabha S, Yamamoto H, Chinni SR, Zhao H, Mobashery S, Vessella RL, Fridman R, Cher ML (2007) Prostate cancer–associated membrane type 1-matrix metalloproteinase: a pivotal role in bone response and intraosseous tumor growth. Am J Pathol 170:2100–2111PubMed Bonfil RD, Dong Z, Trindade Filho JC, Sabbota A, Osenkowski P, Nabha S, Yamamoto H, Chinni SR, Zhao H, Mobashery S, Vessella RL, Fridman R, Cher ML (2007) Prostate cancer–associated membrane type 1-matrix metalloproteinase: a pivotal role in bone response and intraosseous tumor growth. Am J Pathol 170:2100–2111PubMed
71.
Zurück zum Zitat Lynch CC (2011) Matrix metalloproteinases as master regulators of the vicious cycle of bone metastasis. Bone 48:44–53PubMed Lynch CC (2011) Matrix metalloproteinases as master regulators of the vicious cycle of bone metastasis. Bone 48:44–53PubMed
72.
Zurück zum Zitat Thiolloy S, Halpern J, Holt GE, Schwartz HS, Mundy GR, Matrisian LM, Lynch CC (2009) Osteoclast-derived matrix metalloproteinase-7, but not matrix metalloproteinase-9, contributes to tumor-induced osteolysis. Cancer Res 69:6747–6755PubMedCentralPubMed Thiolloy S, Halpern J, Holt GE, Schwartz HS, Mundy GR, Matrisian LM, Lynch CC (2009) Osteoclast-derived matrix metalloproteinase-7, but not matrix metalloproteinase-9, contributes to tumor-induced osteolysis. Cancer Res 69:6747–6755PubMedCentralPubMed
73.
Zurück zum Zitat Divella R, Daniele A, Savino E, Palma F, Bellizzi A, Giotta F, Simone G, Lioce M, Quaranta M, Paradiso A, Mazzocca A (2013) Circulating levels of transforming growth factor-beta (TGF-beta) and chemokine (C-X-C motif) ligand-1 (CXCL1) as predictors of distant seeding of circulating tumor cells in patients with metastatic breast cancer. Anticancer Res 33:1491–1497PubMed Divella R, Daniele A, Savino E, Palma F, Bellizzi A, Giotta F, Simone G, Lioce M, Quaranta M, Paradiso A, Mazzocca A (2013) Circulating levels of transforming growth factor-beta (TGF-beta) and chemokine (C-X-C motif) ligand-1 (CXCL1) as predictors of distant seeding of circulating tumor cells in patients with metastatic breast cancer. Anticancer Res 33:1491–1497PubMed
74.
Zurück zum Zitat McMahon S, Charbonneau M, Grandmont S, Richard DE, Dubois CM (2006) Transforming growth factor beta1 induces hypoxia-inducible factor-1 stabilization through selective inhibition of PHD2 expression. J Biol Chem 281:24171–24181PubMed McMahon S, Charbonneau M, Grandmont S, Richard DE, Dubois CM (2006) Transforming growth factor beta1 induces hypoxia-inducible factor-1 stabilization through selective inhibition of PHD2 expression. J Biol Chem 281:24171–24181PubMed
75.
Zurück zum Zitat Zhang Z, Hu Z, Gupta J, Krimmel JD, Gerseny HM, Berg AF, Robbins JS, Du H, Prabhakar B, Seth P (2012) Intravenous administration of adenoviruses targeting transforming growth factor beta signaling inhibits established bone metastases in 4T1 mouse mammary tumor model in an immunocompetent syngeneic host. Cancer Gene Ther 19:630–636PubMedCentralPubMed Zhang Z, Hu Z, Gupta J, Krimmel JD, Gerseny HM, Berg AF, Robbins JS, Du H, Prabhakar B, Seth P (2012) Intravenous administration of adenoviruses targeting transforming growth factor beta signaling inhibits established bone metastases in 4T1 mouse mammary tumor model in an immunocompetent syngeneic host. Cancer Gene Ther 19:630–636PubMedCentralPubMed
76.
Zurück zum Zitat Feeley BT, Gamradt SC, Hsu WK, Liu N, Krenek L, Robbins P, Huard J, Lieberman JR (2005) Influence of BMPs on the formation of osteoblastic lesions in metastatic prostate cancer. J Bone Miner Res 20:2189–2199PubMed Feeley BT, Gamradt SC, Hsu WK, Liu N, Krenek L, Robbins P, Huard J, Lieberman JR (2005) Influence of BMPs on the formation of osteoblastic lesions in metastatic prostate cancer. J Bone Miner Res 20:2189–2199PubMed
77.
Zurück zum Zitat Barnes J, Anthony CT, Wall N, Steiner MS (1995) Bone morphogenetic protein-6 expression in normal and malignant prostate. World J Urol 13:337–343PubMed Barnes J, Anthony CT, Wall N, Steiner MS (1995) Bone morphogenetic protein-6 expression in normal and malignant prostate. World J Urol 13:337–343PubMed
78.
Zurück zum Zitat Lee YC, Cheng CJ, Bilen MA, Lu JF, Satcher RL, Yu-Lee LY, Gallick GE, Maity SN, Lin SH (2011) BMP4 promotes prostate tumor growth in bone through osteogenesis. Cancer Res 71:5194–5203PubMedCentralPubMed Lee YC, Cheng CJ, Bilen MA, Lu JF, Satcher RL, Yu-Lee LY, Gallick GE, Maity SN, Lin SH (2011) BMP4 promotes prostate tumor growth in bone through osteogenesis. Cancer Res 71:5194–5203PubMedCentralPubMed
79.
Zurück zum Zitat Dai J, Keller J, Zhang J, Lu Y, Yao Z, Keller ET (2005) Bone morphogenetic protein-6 promotes osteoblastic prostate cancer bone metastases through a dual mechanism. Cancer Res 65:8274–8285PubMed Dai J, Keller J, Zhang J, Lu Y, Yao Z, Keller ET (2005) Bone morphogenetic protein-6 promotes osteoblastic prostate cancer bone metastases through a dual mechanism. Cancer Res 65:8274–8285PubMed
80.
Zurück zum Zitat Seckinger A, Meissner T, Moreaux J, Goldschmidt H, Fuhler GM, Benner A, Hundemer M, Reme T, Shaughnessy JD Jr, Barlogie B, Bertsch U, Hillengass J, Ho AD, Pantesco V, Jauch A, De Vos J, Rossi JF, Mohler T, Klein B, Hose D (2009) Bone morphogenic protein 6: a member of a novel class of prognostic factors expressed by normal and malignant plasma cells inhibiting proliferation and angiogenesis. Oncogene 28:3866–3879PubMedCentralPubMed Seckinger A, Meissner T, Moreaux J, Goldschmidt H, Fuhler GM, Benner A, Hundemer M, Reme T, Shaughnessy JD Jr, Barlogie B, Bertsch U, Hillengass J, Ho AD, Pantesco V, Jauch A, De Vos J, Rossi JF, Mohler T, Klein B, Hose D (2009) Bone morphogenic protein 6: a member of a novel class of prognostic factors expressed by normal and malignant plasma cells inhibiting proliferation and angiogenesis. Oncogene 28:3866–3879PubMedCentralPubMed
81.
Zurück zum Zitat Schwaninger R, Rentsch CA, Wetterwald A, van der Horst G, van Bezooijen RL, van der Pluijm G, Lowik CW, Ackermann K, Pyerin W, Hamdy FC, Thalmann GN, Cecchini MG (2007) Lack of noggin expression by cancer cells is a determinant of the osteoblast response in bone metastases. Am J Pathol 170:160–175PubMed Schwaninger R, Rentsch CA, Wetterwald A, van der Horst G, van Bezooijen RL, van der Pluijm G, Lowik CW, Ackermann K, Pyerin W, Hamdy FC, Thalmann GN, Cecchini MG (2007) Lack of noggin expression by cancer cells is a determinant of the osteoblast response in bone metastases. Am J Pathol 170:160–175PubMed
82.
Zurück zum Zitat Rentsch CA, Cecchini MG, Thalmann GN (2009) Loss of inhibition over master pathways of bone mass regulation results in osteosclerotic bone metastases in prostate cancer. Swiss Med Weekly 139:220–225 Rentsch CA, Cecchini MG, Thalmann GN (2009) Loss of inhibition over master pathways of bone mass regulation results in osteosclerotic bone metastases in prostate cancer. Swiss Med Weekly 139:220–225
83.
Zurück zum Zitat Secondini C, Wetterwald A, Schwaninger R, Thalmann GN, Cecchini MG (2011) The role of the BMP signaling antagonist noggin in the development of prostate cancer osteolytic bone metastasis. PloS One 6:e16078PubMedCentralPubMed Secondini C, Wetterwald A, Schwaninger R, Thalmann GN, Cecchini MG (2011) The role of the BMP signaling antagonist noggin in the development of prostate cancer osteolytic bone metastasis. PloS One 6:e16078PubMedCentralPubMed
84.
Zurück zum Zitat Sacchetti B, Funari A, Michienzi S, Di Cesare S, Piersanti S, Saggio I, Tagliafico E, Ferrari S, Robey PG, Riminucci M, Bianco P (2007) Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment. Cell 131:324–336PubMed Sacchetti B, Funari A, Michienzi S, Di Cesare S, Piersanti S, Saggio I, Tagliafico E, Ferrari S, Robey PG, Riminucci M, Bianco P (2007) Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment. Cell 131:324–336PubMed
85.
Zurück zum Zitat Leto G, Incorvaia L, Badalamenti G, Tumminello FM, Gebbia N, Flandina C, Crescimanno M, Rini G (2006) Activin A circulating levels in patients with bone metastasis from breast or prostate cancer. Clin Exp Metastasis 23:117–122PubMed Leto G, Incorvaia L, Badalamenti G, Tumminello FM, Gebbia N, Flandina C, Crescimanno M, Rini G (2006) Activin A circulating levels in patients with bone metastasis from breast or prostate cancer. Clin Exp Metastasis 23:117–122PubMed
86.
Zurück zum Zitat Terpos E, Kastritis E, Christoulas D, Gkotzamanidou M, Eleutherakis-Papaiakovou E, Kanellias N, Papatheodorou A, Dimopoulos MA (2012) Circulating activin-A is elevated in patients with advanced multiple myeloma and correlates with extensive bone involvement and inferior survival; no alterations post-lenalidomide and dexamethasone therapy. Ann Oncol 23:2681–2686PubMed Terpos E, Kastritis E, Christoulas D, Gkotzamanidou M, Eleutherakis-Papaiakovou E, Kanellias N, Papatheodorou A, Dimopoulos MA (2012) Circulating activin-A is elevated in patients with advanced multiple myeloma and correlates with extensive bone involvement and inferior survival; no alterations post-lenalidomide and dexamethasone therapy. Ann Oncol 23:2681–2686PubMed
87.
Zurück zum Zitat Vallet S, Mukherjee S, Vaghela N, Hideshima T, Fulciniti M, Pozzi S, Santo L, Cirstea D, Patel K, Sohani AR, Guimaraes A, Xie W, Chauhan D, Schoonmaker JA, Attar E, Churchill M, Weller E, Munshi N, Seehra JS, Weissleder R, Anderson KC, Scadden DT, Raje N (2010) Activin A promotes multiple myeloma-induced osteolysis and is a promising target for myeloma bone disease. Proc Natl Acad Sci USA 107:5124–5129PubMed Vallet S, Mukherjee S, Vaghela N, Hideshima T, Fulciniti M, Pozzi S, Santo L, Cirstea D, Patel K, Sohani AR, Guimaraes A, Xie W, Chauhan D, Schoonmaker JA, Attar E, Churchill M, Weller E, Munshi N, Seehra JS, Weissleder R, Anderson KC, Scadden DT, Raje N (2010) Activin A promotes multiple myeloma-induced osteolysis and is a promising target for myeloma bone disease. Proc Natl Acad Sci USA 107:5124–5129PubMed
88.
Zurück zum Zitat Nicks KM, Perrien DS, Akel NS, Suva LJ, Gaddy D (2009) Regulation of osteoblastogenesis and osteoclastogenesis by the other reproductive hormones, activin and inhibin. Mol Cell Endocrinol 310:11–20PubMedCentralPubMed Nicks KM, Perrien DS, Akel NS, Suva LJ, Gaddy D (2009) Regulation of osteoblastogenesis and osteoclastogenesis by the other reproductive hormones, activin and inhibin. Mol Cell Endocrinol 310:11–20PubMedCentralPubMed
89.
Zurück zum Zitat Chantry AD, Heath D, Mulivor AW, Pearsall S, Baud’huin M, Coulton L, Evans H, Abdul N, Werner ED, Bouxsein ML, Key ML, Seehra J, Arnett TR, Vanderkerken K, Croucher P (2010) Inhibiting activin-A signaling stimulates bone formation and prevents cancer-induced bone destruction in vivo. J Bone Miner Res 25:2633–2646PubMed Chantry AD, Heath D, Mulivor AW, Pearsall S, Baud’huin M, Coulton L, Evans H, Abdul N, Werner ED, Bouxsein ML, Key ML, Seehra J, Arnett TR, Vanderkerken K, Croucher P (2010) Inhibiting activin-A signaling stimulates bone formation and prevents cancer-induced bone destruction in vivo. J Bone Miner Res 25:2633–2646PubMed
90.
Zurück zum Zitat Tian E, Zhan F, Walker R, Rasmussen E, Ma Y, Barlogie B, Shaughnessy JD Jr (2003) The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. N Engl J Med 349:2483–2494PubMed Tian E, Zhan F, Walker R, Rasmussen E, Ma Y, Barlogie B, Shaughnessy JD Jr (2003) The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. N Engl J Med 349:2483–2494PubMed
91.
Zurück zum Zitat Chen G, Shukeir N, Potti A, Sircar K, Aprikian A, Goltzman D, Rabbani SA (2004) Up-regulation of Wnt-1 and beta-catenin production in patients with advanced metastatic prostate carcinoma: potential pathogenetic and prognostic implications. Cancer 101:1345–1356PubMed Chen G, Shukeir N, Potti A, Sircar K, Aprikian A, Goltzman D, Rabbani SA (2004) Up-regulation of Wnt-1 and beta-catenin production in patients with advanced metastatic prostate carcinoma: potential pathogenetic and prognostic implications. Cancer 101:1345–1356PubMed
92.
Zurück zum Zitat Hall CL, Kang S, MacDougald OA, Keller ET (2006) Role of Wnts in prostate cancer bone metastases. J Cell Biochem 97:661–672PubMed Hall CL, Kang S, MacDougald OA, Keller ET (2006) Role of Wnts in prostate cancer bone metastases. J Cell Biochem 97:661–672PubMed
93.
Zurück zum Zitat Li ZG, Yang J, Vazquez ES, Rose D, Vakar-Lopez F, Mathew P, Lopez A, Logothetis CJ, Lin SH, Navone NM (2008) Low-density lipoprotein receptor-related protein 5 (LRP5) mediates the prostate cancer-induced formation of new bone. Oncogene 27:596–603PubMed Li ZG, Yang J, Vazquez ES, Rose D, Vakar-Lopez F, Mathew P, Lopez A, Logothetis CJ, Lin SH, Navone NM (2008) Low-density lipoprotein receptor-related protein 5 (LRP5) mediates the prostate cancer-induced formation of new bone. Oncogene 27:596–603PubMed
94.
Zurück zum Zitat Thudi NK, Martin CK, Murahari S, Shu ST, Lanigan LG, Werbeck JL, Keller ET, McCauley LK, Pinzone JJ, Rosol TJ (2011) Dickkopf-1 (DKK-1) stimulated prostate cancer growth and metastasis and inhibited bone formation in osteoblastic bone metastases. Prostate 71:615–625PubMedCentralPubMed Thudi NK, Martin CK, Murahari S, Shu ST, Lanigan LG, Werbeck JL, Keller ET, McCauley LK, Pinzone JJ, Rosol TJ (2011) Dickkopf-1 (DKK-1) stimulated prostate cancer growth and metastasis and inhibited bone formation in osteoblastic bone metastases. Prostate 71:615–625PubMedCentralPubMed
95.
Zurück zum Zitat Hall CL, Bafico A, Dai J, Aaronson SA, Keller ET (2005) Prostate cancer cells promote osteoblastic bone metastases through Wnts. Cancer Res 65:7554–7560PubMed Hall CL, Bafico A, Dai J, Aaronson SA, Keller ET (2005) Prostate cancer cells promote osteoblastic bone metastases through Wnts. Cancer Res 65:7554–7560PubMed
96.
Zurück zum Zitat Joesting MS, Perrin S, Elenbaas B, Fawell SE, Rubin JS, Franco OE, Hayward SW, Cunha GR, Marker PC (2005) Identification of SFRP1 as a candidate mediator of stromal-to-epithelial signaling in prostate cancer. Cancer Res 65:10423–10430PubMed Joesting MS, Perrin S, Elenbaas B, Fawell SE, Rubin JS, Franco OE, Hayward SW, Cunha GR, Marker PC (2005) Identification of SFRP1 as a candidate mediator of stromal-to-epithelial signaling in prostate cancer. Cancer Res 65:10423–10430PubMed
97.
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:e3627PubMedCentralPubMed 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:e3627PubMedCentralPubMed
98.
Zurück zum Zitat Voorzanger-Rousselot N, Goehrig D, Journe F, Doriath V, Body JJ, Clezardin P, Garnero P (2007) Increased Dickkopf-1 expression in breast cancer bone metastases. Br J Cancer 97:964–970PubMedCentralPubMed Voorzanger-Rousselot N, Goehrig D, Journe F, Doriath V, Body JJ, Clezardin P, Garnero P (2007) Increased Dickkopf-1 expression in breast cancer bone metastases. Br J Cancer 97:964–970PubMedCentralPubMed
99.
Zurück zum Zitat Bu G, Lu W, Liu CC, Selander K, Yoneda T, Hall C, Keller ET, Li Y (2008) Breast cancer-derived Dickkopf1 inhibits osteoblast differentiation and osteoprotegerin expression: implication for breast cancer osteolytic bone metastases. Int J Cancer 123:1034–1042PubMedCentralPubMed Bu G, Lu W, Liu CC, Selander K, Yoneda T, Hall C, Keller ET, Li Y (2008) Breast cancer-derived Dickkopf1 inhibits osteoblast differentiation and osteoprotegerin expression: implication for breast cancer osteolytic bone metastases. Int J Cancer 123:1034–1042PubMedCentralPubMed
100.
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
101.
Zurück zum Zitat Politou MC, Heath DJ, Rahemtulla A, Szydlo R, Anagnostopoulos A, Dimopoulos MA, Croucher PI, Terpos E (2006) Serum concentrations of Dickkopf-1 protein are increased in patients with multiple myeloma and reduced after autologous stem cell transplantation. Int J Cancer 19:1728–1731 Politou MC, Heath DJ, Rahemtulla A, Szydlo R, Anagnostopoulos A, Dimopoulos MA, Croucher PI, Terpos E (2006) Serum concentrations of Dickkopf-1 protein are increased in patients with multiple myeloma and reduced after autologous stem cell transplantation. Int J Cancer 19:1728–1731
102.
Zurück zum Zitat Giuliani N, Morandi F, Tagliaferri S, Lazzaretti M, Donofrio G, Bonomini S, Sala R, Mangoni M, Rizzoli V (2007) Production of Wnt inhibitors by myeloma cells: potential effects on canonical Wnt pathway in the bone microenvironment. Cancer Res 67:7665–7674PubMed Giuliani N, Morandi F, Tagliaferri S, Lazzaretti M, Donofrio G, Bonomini S, Sala R, Mangoni M, Rizzoli V (2007) Production of Wnt inhibitors by myeloma cells: potential effects on canonical Wnt pathway in the bone microenvironment. Cancer Res 67:7665–7674PubMed
103.
Zurück zum Zitat Fulciniti M, Tassone P, Hideshima T, Vallet S, Nanjappa P, Ettenberg SA, Shen Z, Patel N, Tai YT, Chauhan D, Mitsiades C, Prabhala R, Raje N, Anderson KC, Stover DR, Munshi NC (2009) Anti-DKK1 mAb (BHQ880) as a potential therapeutic agent for multiple myeloma. Blood 114:371–379PubMed Fulciniti M, Tassone P, Hideshima T, Vallet S, Nanjappa P, Ettenberg SA, Shen Z, Patel N, Tai YT, Chauhan D, Mitsiades C, Prabhala R, Raje N, Anderson KC, Stover DR, Munshi NC (2009) Anti-DKK1 mAb (BHQ880) as a potential therapeutic agent for multiple myeloma. Blood 114:371–379PubMed
104.
Zurück zum Zitat Oshima T, Abe M, Asano J, Hara T, Kitazoe K, Sekimoto E, Tanaka Y, Shibata H, Hashimoto T, Ozaki S, Kido S, Inoue D, Matsumoto T (2005) Myeloma cells suppress bone formation by secreting a soluble Wnt inhibitor, sFRP-2. Blood 106:3160–3165PubMed Oshima T, Abe M, Asano J, Hara T, Kitazoe K, Sekimoto E, Tanaka Y, Shibata H, Hashimoto T, Ozaki S, Kido S, Inoue D, Matsumoto T (2005) Myeloma cells suppress bone formation by secreting a soluble Wnt inhibitor, sFRP-2. Blood 106:3160–3165PubMed
105.
Zurück zum Zitat Qiang YW, Barlogie B, Rudikoff S, Shaughnessy JD Jr (2008) Dkk1-induced inhibition of Wnt signaling in osteoblast differentiation is an underlying mechanism of bone loss in multiple myeloma. Bone 42:669–680PubMed Qiang YW, Barlogie B, Rudikoff S, Shaughnessy JD Jr (2008) Dkk1-induced inhibition of Wnt signaling in osteoblast differentiation is an underlying mechanism of bone loss in multiple myeloma. Bone 42:669–680PubMed
106.
Zurück zum Zitat Fowler JA, Mundy GR, Lwin ST, Edwards CM (2012) Bone marrow stromal cells create a permissive microenvironment for myeloma development: a new stromal role for Wnt inhibitor Dkk1. Cancer Res 72:2183–2189PubMedCentralPubMed Fowler JA, Mundy GR, Lwin ST, Edwards CM (2012) Bone marrow stromal cells create a permissive microenvironment for myeloma development: a new stromal role for Wnt inhibitor Dkk1. Cancer Res 72:2183–2189PubMedCentralPubMed
107.
Zurück zum Zitat Kim Y, Reifenberger G, Lu D, Endo T, Carson DA, Gast SM, Meschenmoser K, Nowak M, Schmidt-Wolf IG (2011) Influencing the Wnt signaling pathway in multiple myeloma. Anticancer Res 31:725–730PubMed Kim Y, Reifenberger G, Lu D, Endo T, Carson DA, Gast SM, Meschenmoser K, Nowak M, Schmidt-Wolf IG (2011) Influencing the Wnt signaling pathway in multiple myeloma. Anticancer Res 31:725–730PubMed
108.
Zurück zum Zitat Yaccoby S, Ling W, Zhan F, Walker R, Barlogie B, Shaughnessy JD Jr (2007) Antibody-based inhibition of DKK1 suppresses tumor-induced bone resorption and multiple myeloma growth in vivo. Blood 109:2106–2111PubMed Yaccoby S, Ling W, Zhan F, Walker R, Barlogie B, Shaughnessy JD Jr (2007) Antibody-based inhibition of DKK1 suppresses tumor-induced bone resorption and multiple myeloma growth in vivo. Blood 109:2106–2111PubMed
109.
Zurück zum Zitat Heath DJ, Chantry AD, Buckle CH, Coulton L, Shaughnessy JD Jr, Evans HR, Snowden JA, Stover DR, Vanderkerken K, Croucher PI (2009) Inhibiting Dickkopf-1 (Dkk1) removes suppression of bone formation and prevents the development of osteolytic bone disease in multiple myeloma. J Bone Miner Res 24:425–436PubMed Heath DJ, Chantry AD, Buckle CH, Coulton L, Shaughnessy JD Jr, Evans HR, Snowden JA, Stover DR, Vanderkerken K, Croucher PI (2009) Inhibiting Dickkopf-1 (Dkk1) removes suppression of bone formation and prevents the development of osteolytic bone disease in multiple myeloma. J Bone Miner Res 24:425–436PubMed
110.
Zurück zum Zitat Edwards CM, Edwards JR, Lwin ST, Esparza J, Oyajobi BO, McCluskey B, Munoz S, Grubbs B, Mundy GR (2008) Increasing Wnt signaling in the bone marrow microenvironment inhibits the development of myeloma bone disease and reduces tumor burden in bone in vivo. Blood 111:2833–2842PubMed Edwards CM, Edwards JR, Lwin ST, Esparza J, Oyajobi BO, McCluskey B, Munoz S, Grubbs B, Mundy GR (2008) Increasing Wnt signaling in the bone marrow microenvironment inhibits the development of myeloma bone disease and reduces tumor burden in bone in vivo. Blood 111:2833–2842PubMed
111.
Zurück zum Zitat Colucci S, Brunetti G, Oranger A, Mori G, Sardone F, Specchia G, Rinaldi E, Curci P, Liso V, Passeri G, Zallone A, Rizzi R, Grano M (2011) Myeloma cells suppress osteoblasts through sclerostin secretion. Blood Cancer J 1:e27PubMedCentralPubMed Colucci S, Brunetti G, Oranger A, Mori G, Sardone F, Specchia G, Rinaldi E, Curci P, Liso V, Passeri G, Zallone A, Rizzi R, Grano M (2011) Myeloma cells suppress osteoblasts through sclerostin secretion. Blood Cancer J 1:e27PubMedCentralPubMed
112.
Zurück zum Zitat Terpos E, Christoulas D, Katodritou E, Bratengeier C, Gkotzamanidou M, Michalis E, Delimpasi S, Pouli A, Meletis J, Kastritis E, Zervas K, Dimopoulos MA (2012) Elevated circulating sclerostin correlates with advanced disease features and abnormal bone remodeling in symptomatic myeloma: reduction post-bortezomib monotherapy. Int J Cancer 131:1466–1471PubMed Terpos E, Christoulas D, Katodritou E, Bratengeier C, Gkotzamanidou M, Michalis E, Delimpasi S, Pouli A, Meletis J, Kastritis E, Zervas K, Dimopoulos MA (2012) Elevated circulating sclerostin correlates with advanced disease features and abnormal bone remodeling in symptomatic myeloma: reduction post-bortezomib monotherapy. Int J Cancer 131:1466–1471PubMed
113.
Zurück zum Zitat Gkotzamanidou M, Dimopoulos MA, Kastritis E, Christoulas D, Moulopoulos LA, Terpos E (2012) Sclerostin: a possible target for the management of cancer-induced bone disease. Expert Opin Ther Targets 16:761–769PubMed Gkotzamanidou M, Dimopoulos MA, Kastritis E, Christoulas D, Moulopoulos LA, Terpos E (2012) Sclerostin: a possible target for the management of cancer-induced bone disease. Expert Opin Ther Targets 16:761–769PubMed
114.
Zurück zum Zitat Mendoza-Villanueva D, Zeef L, Shore P (2011) Metastatic breast cancer cells inhibit osteoblast differentiation through the Runx2/CBFbeta-dependent expression of the Wnt antagonist, sclerostin. Breast Cancer Res 13:R106PubMedCentralPubMed Mendoza-Villanueva D, Zeef L, Shore P (2011) Metastatic breast cancer cells inhibit osteoblast differentiation through the Runx2/CBFbeta-dependent expression of the Wnt antagonist, sclerostin. Breast Cancer Res 13:R106PubMedCentralPubMed
115.
Zurück zum Zitat Meyers KE, Sethna C (2013) Endothelin antagonists in hypertension and kidney disease. Pediatr Nephrol 28:711–720PubMed Meyers KE, Sethna C (2013) Endothelin antagonists in hypertension and kidney disease. Pediatr Nephrol 28:711–720PubMed
116.
Zurück zum Zitat Clines GA, Mohammad KS, Grunda JM, Clines KL, Niewolna M, McKenna CR, McKibbin CR, Yanagisawa M, Suva LJ, Chirgwin JM, Guise TA (2011) Regulation of postnatal trabecular bone formation by the osteoblast endothelin A receptor. J Bone Miner Res 26:2523–2536PubMedCentralPubMed Clines GA, Mohammad KS, Grunda JM, Clines KL, Niewolna M, McKenna CR, McKibbin CR, Yanagisawa M, Suva LJ, Chirgwin JM, Guise TA (2011) Regulation of postnatal trabecular bone formation by the osteoblast endothelin A receptor. J Bone Miner Res 26:2523–2536PubMedCentralPubMed
117.
Zurück zum Zitat Guise TA, Mohammad KS (2004) Endothelins in bone cancer metastases. Cancer Treat Res 118:197–212PubMed Guise TA, Mohammad KS (2004) Endothelins in bone cancer metastases. Cancer Treat Res 118:197–212PubMed
118.
Zurück zum Zitat Nelson JB, Hedican SP, George DJ, Reddi AH, Piantadosi S, Eisenberger MA, Simons JW (1995) Identification of endothelin-1 in the pathophysiology of metastatic adenocarcinoma of the prostate. Nat Med 1:944–949PubMed Nelson JB, Hedican SP, George DJ, Reddi AH, Piantadosi S, Eisenberger MA, Simons JW (1995) Identification of endothelin-1 in the pathophysiology of metastatic adenocarcinoma of the prostate. Nat Med 1:944–949PubMed
119.
Zurück zum Zitat Yin JJ, Mohammad KS, Kakonen SM, Harris S, Wu-Wong JR, Wessale JL, Padley RJ, Garrett IR, Chirgwin JM, Guise TA (2003) A causal role for endothelin-1 in the pathogenesis of osteoblastic bone metastases. Proc Natl Acad Sci USA 100:10954–10959PubMed Yin JJ, Mohammad KS, Kakonen SM, Harris S, Wu-Wong JR, Wessale JL, Padley RJ, Garrett IR, Chirgwin JM, Guise TA (2003) A causal role for endothelin-1 in the pathogenesis of osteoblastic bone metastases. Proc Natl Acad Sci USA 100:10954–10959PubMed
120.
Zurück zum Zitat Carducci MA, Saad F, Abrahamsson PA, Dearnaley DP, Schulman CC, North SA, Sleep DJ, Isaacson JD, Nelson JB, Atrasentan Phase III, Institutions Study Group (2007) A phase 3 randomized controlled trial of the efficacy and safety of atrasentan in men with metastatic hormone-refractory prostate cancer. Cancer 110:1959–1966PubMed Carducci MA, Saad F, Abrahamsson PA, Dearnaley DP, Schulman CC, North SA, Sleep DJ, Isaacson JD, Nelson JB, Atrasentan Phase III, Institutions Study Group (2007) A phase 3 randomized controlled trial of the efficacy and safety of atrasentan in men with metastatic hormone-refractory prostate cancer. Cancer 110:1959–1966PubMed
121.
Zurück zum Zitat James ND, Caty A, Borre M, Zonnenberg BA, Beuzeboc P, Morris T, Phung D, Dawson NA (2009) Safety and efficacy of the specific endothelin-A receptor antagonist ZD4054 in patients with hormone-resistant prostate cancer and bone metastases who were pain free or mildly symptomatic: a double-blind, placebo-controlled, randomised, phase 2 trial. Eur Urol 55:1112–1123PubMed James ND, Caty A, Borre M, Zonnenberg BA, Beuzeboc P, Morris T, Phung D, Dawson NA (2009) Safety and efficacy of the specific endothelin-A receptor antagonist ZD4054 in patients with hormone-resistant prostate cancer and bone metastases who were pain free or mildly symptomatic: a double-blind, placebo-controlled, randomised, phase 2 trial. Eur Urol 55:1112–1123PubMed
122.
Zurück zum Zitat Tokuda H, Hanai Y, Matsushima-Nishiwaki R, Yamauchi J, Doi T, Harada A, Takai S, Kozawa O (2007) Rho-kinase regulates endothelin-1-stimulated IL-6 synthesis via p38 MAP kinase in osteoblasts. Biochem Biophys Res Commun 362:799–804PubMed Tokuda H, Hanai Y, Matsushima-Nishiwaki R, Yamauchi J, Doi T, Harada A, Takai S, Kozawa O (2007) Rho-kinase regulates endothelin-1-stimulated IL-6 synthesis via p38 MAP kinase in osteoblasts. Biochem Biophys Res Commun 362:799–804PubMed
123.
Zurück zum Zitat Ogawa K, Pasqualini R, Lindberg RA, Kain R, Freeman AL, Pasquale EB (2000) The ephrin-A1 ligand and its receptor, EphA2, are expressed during tumor neovascularization. Oncogene 19:6043–6052PubMed Ogawa K, Pasqualini R, Lindberg RA, Kain R, Freeman AL, Pasquale EB (2000) The ephrin-A1 ligand and its receptor, EphA2, are expressed during tumor neovascularization. Oncogene 19:6043–6052PubMed
124.
Zurück zum Zitat Zelinski DP, Zantek ND, Stewart JC, Irizarry AR, Kinch MS (2001) EphA2 overexpression causes tumorigenesis of mammary epithelial cells. Cancer Res 61:2301–2306PubMed Zelinski DP, Zantek ND, Stewart JC, Irizarry AR, Kinch MS (2001) EphA2 overexpression causes tumorigenesis of mammary epithelial cells. Cancer Res 61:2301–2306PubMed
125.
Zurück zum Zitat Irie N, Takada Y, Watanabe Y, Matsuzaki Y, Naruse C, Asano M, Iwakura Y, Suda T, Matsuo K (2009) Bidirectional signaling through ephrinA2-EphA2 enhances osteoclastogenesis and suppresses osteoblastogenesis. J Biol Chem 284:14637–14644PubMed Irie N, Takada Y, Watanabe Y, Matsuzaki Y, Naruse C, Asano M, Iwakura Y, Suda T, Matsuo K (2009) Bidirectional signaling through ephrinA2-EphA2 enhances osteoclastogenesis and suppresses osteoblastogenesis. J Biol Chem 284:14637–14644PubMed
126.
Zurück zum Zitat Pennisi A, Ling W, Li X, Khan S, Shaughnessy JD Jr, Barlogie B, Yaccoby S (2009) The ephrinB2/EphB4 axis is dysregulated in osteoprogenitors from myeloma patients and its activation affects myeloma bone disease and tumor growth. Blood 114:1803–1812PubMed Pennisi A, Ling W, Li X, Khan S, Shaughnessy JD Jr, Barlogie B, Yaccoby S (2009) The ephrinB2/EphB4 axis is dysregulated in osteoprogenitors from myeloma patients and its activation affects myeloma bone disease and tumor growth. Blood 114:1803–1812PubMed
127.
Zurück zum Zitat Coltrera MD, Wang J, Porter PL, Gown AM (1995) Expression of platelet-derived growth factor B-chain and the platelet-derived growth factor receptor beta subunit in human breast tissue and breast carcinoma. Cancer Res 55:2703–2708PubMed Coltrera MD, Wang J, Porter PL, Gown AM (1995) Expression of platelet-derived growth factor B-chain and the platelet-derived growth factor receptor beta subunit in human breast tissue and breast carcinoma. Cancer Res 55:2703–2708PubMed
128.
Zurück zum Zitat Seymour L, Dajee D, Bezwoda WR (1993) Tissue platelet-derived growth factor (PDGF) predicts for shortened survival and treatment failure in advanced breast cancer. Breast Cancer Res Treat 26:247–252PubMed Seymour L, Dajee D, Bezwoda WR (1993) Tissue platelet-derived growth factor (PDGF) predicts for shortened survival and treatment failure in advanced breast cancer. Breast Cancer Res Treat 26:247–252PubMed
129.
Zurück zum Zitat Canalis E, Rydziel S (1996) Platelet-derived growth factor and the skeleton. In: Bilezikian JB, Raisz LG, Rodan A (eds) Principles of bone biology. Academic Press, San Diego, CA, pp 619–626 Canalis E, Rydziel S (1996) Platelet-derived growth factor and the skeleton. In: Bilezikian JB, Raisz LG, Rodan A (eds) Principles of bone biology. Academic Press, San Diego, CA, pp 619–626
130.
Zurück zum Zitat Vordemvenne T, Paletta JR, Hartensuer R, Pap T, Raschke MJ, Ochman S (2011) Cooperative effects in differentiation and proliferation between PDGF-BB and matrix derived synthetic peptides in human osteoblasts. BMC Musculoskelet Disord 12:263PubMedCentralPubMed Vordemvenne T, Paletta JR, Hartensuer R, Pap T, Raschke MJ, Ochman S (2011) Cooperative effects in differentiation and proliferation between PDGF-BB and matrix derived synthetic peptides in human osteoblasts. BMC Musculoskelet Disord 12:263PubMedCentralPubMed
131.
Zurück zum Zitat Franchimont N, Canalis E (1995) Platelet-derived growth factor stimulates the synthesis of interleukin-6 in cells of the osteoblast lineage. Endocrinology 136:5469–5475PubMed Franchimont N, Canalis E (1995) Platelet-derived growth factor stimulates the synthesis of interleukin-6 in cells of the osteoblast lineage. Endocrinology 136:5469–5475PubMed
132.
Zurück zum Zitat Hamdan R, Zhou Z, Kleinerman ES (2011) SDF-1alpha induces PDGF-B expression and the differentiation of bone marrow cells into pericytes. Mol Cancer Res 9:1462–1470PubMedCentralPubMed Hamdan R, Zhou Z, Kleinerman ES (2011) SDF-1alpha induces PDGF-B expression and the differentiation of bone marrow cells into pericytes. Mol Cancer Res 9:1462–1470PubMedCentralPubMed
133.
Zurück zum Zitat Xue Y, Lim S, Yang Y, Wang Z, Jensen LD, Hedlund EM, Andersson P, Sasahara M, Larsson O, Galter D, Cao R, Hosaka K, Cao Y (2012) PDGF-BB modulates hematopoiesis and tumor angiogenesis by inducing erythropoietin production in stromal cells. Nat Med 18:100–110 Xue Y, Lim S, Yang Y, Wang Z, Jensen LD, Hedlund EM, Andersson P, Sasahara M, Larsson O, Galter D, Cao R, Hosaka K, Cao Y (2012) PDGF-BB modulates hematopoiesis and tumor angiogenesis by inducing erythropoietin production in stromal cells. Nat Med 18:100–110
134.
Zurück zum Zitat Valta MP, Hentunen T, Qu Q, Valve EM, Harjula A, Seppanen JA, Vaananen HK, Harkonen PL (2006) Regulation of osteoblast differentiation: a novel function for fibroblast growth factor 8. Endocrinology 147:2171–2182PubMed Valta MP, Hentunen T, Qu Q, Valve EM, Harjula A, Seppanen JA, Vaananen HK, Harkonen PL (2006) Regulation of osteoblast differentiation: a novel function for fibroblast growth factor 8. Endocrinology 147:2171–2182PubMed
135.
Zurück zum Zitat Kitagawa Y, Dai J, Zhang J, Keller JM, Nor J, Yao Z, Keller ET (2005) Vascular endothelial growth factor contributes to prostate cancer–mediated osteoblastic activity. Cancer Res 65:10921–10929PubMed Kitagawa Y, Dai J, Zhang J, Keller JM, Nor J, Yao Z, Keller ET (2005) Vascular endothelial growth factor contributes to prostate cancer–mediated osteoblastic activity. Cancer Res 65:10921–10929PubMed
136.
Zurück zum Zitat DeNardo DG, Andreu P, Coussens LM (2010) Interactions between lymphocytes and myeloid cells regulate pro- versus anti-tumor immunity. Cancer Metastasis Rev 29:309–316PubMedCentralPubMed DeNardo DG, Andreu P, Coussens LM (2010) Interactions between lymphocytes and myeloid cells regulate pro- versus anti-tumor immunity. Cancer Metastasis Rev 29:309–316PubMedCentralPubMed
137.
Zurück zum Zitat Noonan K, Marchionni L, Anderson J, Pardoll D, Roodman GD, Borrello I (2010) A novel role of IL-17-producing lymphocytes in mediating lytic bone disease in multiple myeloma. Blood 116:3554–3563PubMed Noonan K, Marchionni L, Anderson J, Pardoll D, Roodman GD, Borrello I (2010) A novel role of IL-17-producing lymphocytes in mediating lytic bone disease in multiple myeloma. Blood 116:3554–3563PubMed
138.
Zurück zum Zitat Zhao E, Wang L, Dai J, Kryczek I, Wei S, Vatan L, Altuwaijri S, Sparwasser T, Wang G, Keller ET, Zou W (2012) Regulatory T cells in the bone marrow microenvironment in patients with prostate cancer. Oncoimmunology 1:152–161PubMedCentralPubMed Zhao E, Wang L, Dai J, Kryczek I, Wei S, Vatan L, Altuwaijri S, Sparwasser T, Wang G, Keller ET, Zou W (2012) Regulatory T cells in the bone marrow microenvironment in patients with prostate cancer. Oncoimmunology 1:152–161PubMedCentralPubMed
139.
Zurück zum Zitat Sawant A, Hensel JA, Chanda D, Harris BA, Siegal GP, Maheshwari A, Ponnazhagan S (2012) Depletion of plasmacytoid dendritic cells inhibits tumor growth and prevents bone metastasis of breast cancer cells. J Immunol 189:4258–4265PubMedCentralPubMed Sawant A, Hensel JA, Chanda D, Harris BA, Siegal GP, Maheshwari A, Ponnazhagan S (2012) Depletion of plasmacytoid dendritic cells inhibits tumor growth and prevents bone metastasis of breast cancer cells. J Immunol 189:4258–4265PubMedCentralPubMed
140.
Zurück zum Zitat Zirakzadeh AA, Marits P, Sherif A, Winqvist O (2013) Multiplex B cell characterization in blood, lymph nodes, and tumors from patients with malignancies. J Immunol 190:5847–5855PubMed Zirakzadeh AA, Marits P, Sherif A, Winqvist O (2013) Multiplex B cell characterization in blood, lymph nodes, and tumors from patients with malignancies. J Immunol 190:5847–5855PubMed
141.
Zurück zum Zitat Shah S, Divekar AA, Hilchey SP, Cho HM, Newman CL, Shin SU, Nechustan H, Challita-Eid PM, Segal BM, Yi KH, Rosenblatt JD (2005) Increased rejection of primary tumors in mice lacking B cells: inhibition of anti-tumor CTL and TH1 cytokine responses by B cells. Int J Cancer 117:574–586PubMed Shah S, Divekar AA, Hilchey SP, Cho HM, Newman CL, Shin SU, Nechustan H, Challita-Eid PM, Segal BM, Yi KH, Rosenblatt JD (2005) Increased rejection of primary tumors in mice lacking B cells: inhibition of anti-tumor CTL and TH1 cytokine responses by B cells. Int J Cancer 117:574–586PubMed
142.
Zurück zum Zitat Yun TJ, Chaudhary PM, Shu GL, Frazer JK, Ewings MK, Schwartz SM, Pascual V, Hood LE, Clark EA (1998) OPG/FDCR-1, a TNF receptor family member, is expressed in lymphoid cells and is up-regulated by ligating CD40. J Immunol 161:6113–6121PubMed Yun TJ, Chaudhary PM, Shu GL, Frazer JK, Ewings MK, Schwartz SM, Pascual V, Hood LE, Clark EA (1998) OPG/FDCR-1, a TNF receptor family member, is expressed in lymphoid cells and is up-regulated by ligating CD40. J Immunol 161:6113–6121PubMed
143.
Zurück zum Zitat Youn JI, Gabrilovich DI (2010) The biology of myeloid-derived suppressor cells: the blessing and the curse of morphological and functional heterogeneity. Eur J Immunol 40:2969–2975PubMedCentralPubMed Youn JI, Gabrilovich DI (2010) The biology of myeloid-derived suppressor cells: the blessing and the curse of morphological and functional heterogeneity. Eur J Immunol 40:2969–2975PubMedCentralPubMed
144.
Zurück zum Zitat Danilin S, Merkel AR, Johnson JR, Johnson RW, Edwards JR, Sterling JA (2012) Myeloid-derived suppressor cells expand during breast cancer progression and promote tumor-induced bone destruction. Oncoimmunology 1:1484–1494PubMedCentralPubMed Danilin S, Merkel AR, Johnson JR, Johnson RW, Edwards JR, Sterling JA (2012) Myeloid-derived suppressor cells expand during breast cancer progression and promote tumor-induced bone destruction. Oncoimmunology 1:1484–1494PubMedCentralPubMed
145.
Zurück zum Zitat Zhuang J, Zhang J, Lwin ST, Edwards JR, Edwards CM, Mundy GR, Yang X (2012) Osteoclasts in multiple myeloma are derived from Gr-1+CD11b+myeloid-derived suppressor cells. PloS One 7:e48871PubMedCentralPubMed Zhuang J, Zhang J, Lwin ST, Edwards JR, Edwards CM, Mundy GR, Yang X (2012) Osteoclasts in multiple myeloma are derived from Gr-1+CD11b+myeloid-derived suppressor cells. PloS One 7:e48871PubMedCentralPubMed
Metadaten
Titel
Signaling Between Tumor Cells and the Host Bone Marrow Microenvironment
verfasst von
Natasa Kovacic
Peter I. Croucher
Michelle M. McDonald
Publikationsdatum
01.01.2014
Verlag
Springer US
Erschienen in
Calcified Tissue International / Ausgabe 1/2014
Print ISSN: 0171-967X
Elektronische ISSN: 1432-0827
DOI
https://doi.org/10.1007/s00223-013-9794-7

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