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Erschienen in: Breast Cancer Research 3/2007

01.06.2007 | Review

Inflammation and breast cancer. Microenvironmental factors regulating macrophage function in breast tumours: hypoxia and angiopoietin-2

verfasst von: Claire E Lewis, Russell Hughes

Erschienen in: Breast Cancer Research | Ausgabe 3/2007

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Abstract

Considerable evidence has now accumulated for tumour-associated macrophages stimulating key aspects of tumour progression, including the proliferation, survival and metastasis of tumour cells, tumour angiogenesis and suppression of the anti-tumour functions of other immune effectors at the tumour site. Tumour micro-environmental factors such as hypoxia have profound, direct effects on these cells, stimulating many of their pro-tumour functions. Hypoxia also does so indirectly by stimulating the release of the cytokine angiopoietin-2 from tumour cells and tumour blood vessels. This in turn then recruits Tie-2-expressing monocytes into tumours from the bloodstream and inhibits their production of anti-apoptotic and anti-angiogenic cytokines.
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Literatur
1.
Zurück zum Zitat Lin EY, Nguyen AV, Russell RG, Pollard JW: Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy. J Exp Med. 2001, 193: 727-740. 10.1084/jem.193.6.727.CrossRefPubMedPubMedCentral Lin EY, Nguyen AV, Russell RG, Pollard JW: Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy. J Exp Med. 2001, 193: 727-740. 10.1084/jem.193.6.727.CrossRefPubMedPubMedCentral
2.
Zurück zum Zitat Bingle L, Brown NJ, Lewis CE: The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies. J Pathol. 2002, 196: 254-265. 10.1002/path.1027.CrossRefPubMed Bingle L, Brown NJ, Lewis CE: The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies. J Pathol. 2002, 196: 254-265. 10.1002/path.1027.CrossRefPubMed
3.
Zurück zum Zitat Lewis CE, Pollard JW: Distinct role of macrophages in different tumor microenvironments. Cancer Res. 2006, 66: 605-612. 10.1158/0008-5472.CAN-05-4005.CrossRefPubMed Lewis CE, Pollard JW: Distinct role of macrophages in different tumor microenvironments. Cancer Res. 2006, 66: 605-612. 10.1158/0008-5472.CAN-05-4005.CrossRefPubMed
4.
Zurück zum Zitat Lin EY, Li JF, Gnatovskiy L, Deng Y, Zhu L, Grzesik DA, Qian H, Xue XN, Pollard JW: Macrophages regulate the angiogenic switch in a mouse model of breast cancer. Cancer Res. 2006, 66: 11238-11246. 10.1158/0008-5472.CAN-06-1278.CrossRefPubMed Lin EY, Li JF, Gnatovskiy L, Deng Y, Zhu L, Grzesik DA, Qian H, Xue XN, Pollard JW: Macrophages regulate the angiogenic switch in a mouse model of breast cancer. Cancer Res. 2006, 66: 11238-11246. 10.1158/0008-5472.CAN-06-1278.CrossRefPubMed
5.
Zurück zum Zitat Leek RD, Lewis CE, Whitehouse R, Greenall M, Clarke J, Harris AL: Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma. Cancer Res. 1996, 56: 4625-4629.PubMed Leek RD, Lewis CE, Whitehouse R, Greenall M, Clarke J, Harris AL: Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma. Cancer Res. 1996, 56: 4625-4629.PubMed
6.
Zurück zum Zitat O'Sullivan C, Lewis CE, Harris AL, McGee JO: Secretion of epidermal growth factor by macrophages associated with breast carcinoma. Lancet. 1993, 342: 148-149. 10.1016/0140-6736(93)91348-P.CrossRefPubMed O'Sullivan C, Lewis CE, Harris AL, McGee JO: Secretion of epidermal growth factor by macrophages associated with breast carcinoma. Lancet. 1993, 342: 148-149. 10.1016/0140-6736(93)91348-P.CrossRefPubMed
7.
Zurück zum Zitat Lewis JS, Landers RJ, Underwood JC, Harris AL, Lewis CE: Expression of vascular endothelial growth factor by macrophages is up-regulated in poorly vascularized areas of breast carcinomas. J Pathol. 2000, 192: 150-158. 10.1002/1096-9896(2000)9999:9999<::AID-PATH687>3.0.CO;2-G.CrossRefPubMed Lewis JS, Landers RJ, Underwood JC, Harris AL, Lewis CE: Expression of vascular endothelial growth factor by macrophages is up-regulated in poorly vascularized areas of breast carcinomas. J Pathol. 2000, 192: 150-158. 10.1002/1096-9896(2000)9999:9999<::AID-PATH687>3.0.CO;2-G.CrossRefPubMed
8.
Zurück zum Zitat Mantovani A, Schioppa T, Porta C, Allavena P, Sica A: Role of tumor-associated macrophages in tumor progression and invasion. Cancer Metastasis Rev. 2006, 25: 315-322. 10.1007/s10555-006-9001-7.CrossRefPubMed Mantovani A, Schioppa T, Porta C, Allavena P, Sica A: Role of tumor-associated macrophages in tumor progression and invasion. Cancer Metastasis Rev. 2006, 25: 315-322. 10.1007/s10555-006-9001-7.CrossRefPubMed
9.
Zurück zum Zitat Sica A, Saccani A, Bottazzi B, Polentarutti N, Vecchi A, van Damme J, Mantovani A: Autocrine production of IL-10 mediates defective IL-12 production and NF-κB activation in tumor-associated macrophages. J Immunol. 2000, 164: 762-767.CrossRefPubMed Sica A, Saccani A, Bottazzi B, Polentarutti N, Vecchi A, van Damme J, Mantovani A: Autocrine production of IL-10 mediates defective IL-12 production and NF-κB activation in tumor-associated macrophages. J Immunol. 2000, 164: 762-767.CrossRefPubMed
10.
Zurück zum Zitat Vaupel P, Schlenger K, Knoop C, Hockel M: Oxygenation of human tumors: evaluation of tissue oxygen distribution in breast cancers by computerized O2 tension measurements. Cancer Res. 1991, 51: 3316-3322.PubMed Vaupel P, Schlenger K, Knoop C, Hockel M: Oxygenation of human tumors: evaluation of tissue oxygen distribution in breast cancers by computerized O2 tension measurements. Cancer Res. 1991, 51: 3316-3322.PubMed
11.
Zurück zum Zitat Holmquist L, Lofstedt T, Pahlman S: Effect of hypoxia on the tumor phenotype: the neuroblastoma and breast cancer models. Adv Exp Med Biol. 2006, 587: 179-193.CrossRefPubMed Holmquist L, Lofstedt T, Pahlman S: Effect of hypoxia on the tumor phenotype: the neuroblastoma and breast cancer models. Adv Exp Med Biol. 2006, 587: 179-193.CrossRefPubMed
12.
Zurück zum Zitat Leek RD, Landers RJ, Harris AL, Lewis CE: Necrosis correlates with high vascular density and focal macrophage infiltration in invasive carcinoma of the breast. Br J Cancer. 1999, 79: 991-995. 10.1038/sj.bjc.6690158.CrossRefPubMedPubMedCentral Leek RD, Landers RJ, Harris AL, Lewis CE: Necrosis correlates with high vascular density and focal macrophage infiltration in invasive carcinoma of the breast. Br J Cancer. 1999, 79: 991-995. 10.1038/sj.bjc.6690158.CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Murdoch C, Giannoudis A, Lewis CE: Mechanisms regulating the recruitment of macrophages into hypoxic areas of tumors and other ischemic tissues. Blood. 2004, 104: 2224-2234. 10.1182/blood-2004-03-1109.CrossRefPubMed Murdoch C, Giannoudis A, Lewis CE: Mechanisms regulating the recruitment of macrophages into hypoxic areas of tumors and other ischemic tissues. Blood. 2004, 104: 2224-2234. 10.1182/blood-2004-03-1109.CrossRefPubMed
14.
Zurück zum Zitat Turner L, Scotton C, Negus R, Balkwill F: Hypoxia inhibits macrophage migration. Eur J Immunol. 1999, 29: 2280-2287. 10.1002/(SICI)1521-4141(199907)29:07<2280::AID-IMMU2280>3.0.CO;2-C.CrossRefPubMed Turner L, Scotton C, Negus R, Balkwill F: Hypoxia inhibits macrophage migration. Eur J Immunol. 1999, 29: 2280-2287. 10.1002/(SICI)1521-4141(199907)29:07<2280::AID-IMMU2280>3.0.CO;2-C.CrossRefPubMed
15.
Zurück zum Zitat Burke B, Giannoudis A, Corke KP, Gill D, Wells M, Ziegler-Heitbrock L, Lewis CE: Hypoxia-induced gene expression in human macrophages: implications for ischemic tissues and hypoxia-regulated gene therapy. Am J Pathol. 2003, 163: 1233-1243.CrossRefPubMedPubMedCentral Burke B, Giannoudis A, Corke KP, Gill D, Wells M, Ziegler-Heitbrock L, Lewis CE: Hypoxia-induced gene expression in human macrophages: implications for ischemic tissues and hypoxia-regulated gene therapy. Am J Pathol. 2003, 163: 1233-1243.CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Bingle L, Lewis CE, Corke KP, Reed MW, Brown NJ: Macrophages promote angiogenesis in human breast tumour spheroids in vivo. Br J Cancer. 2006, 94: 101-107. 10.1038/sj.bjc.6602901.CrossRefPubMedPubMedCentral Bingle L, Lewis CE, Corke KP, Reed MW, Brown NJ: Macrophages promote angiogenesis in human breast tumour spheroids in vivo. Br J Cancer. 2006, 94: 101-107. 10.1038/sj.bjc.6602901.CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat White JR, Harris RA, Lee SR, Craigon MH, Binley K, Price T, Beard L, Mundy CR, Naylor S: Genetic amplification of the transcriptional response to hypoxia as a novel means of identifying regulators of angiogenesis. Genomics. 2004, 83: 1-8. 10.1016/S0888-7543(03)00215-5.CrossRefPubMed White JR, Harris RA, Lee SR, Craigon MH, Binley K, Price T, Beard L, Mundy CR, Naylor S: Genetic amplification of the transcriptional response to hypoxia as a novel means of identifying regulators of angiogenesis. Genomics. 2004, 83: 1-8. 10.1016/S0888-7543(03)00215-5.CrossRefPubMed
18.
Zurück zum Zitat Lewis C, Murdoch C: Macrophage responses to hypoxia: implications for tumor progression and anti-cancer therapies. Am J Pathol. 2005, 167: 627-635.CrossRefPubMedPubMedCentral Lewis C, Murdoch C: Macrophage responses to hypoxia: implications for tumor progression and anti-cancer therapies. Am J Pathol. 2005, 167: 627-635.CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Burke B, Tang N, Corke KP, Tazzyman D, Ameri K, Wells M, Lewis CE: Expression of HIF-1α by human macrophages: implications for the use of macrophages in hypoxia-regulated cancer gene therapy. J Pathol. 2002, 196: 204-212. 10.1002/path.1029.CrossRefPubMed Burke B, Tang N, Corke KP, Tazzyman D, Ameri K, Wells M, Lewis CE: Expression of HIF-1α by human macrophages: implications for the use of macrophages in hypoxia-regulated cancer gene therapy. J Pathol. 2002, 196: 204-212. 10.1002/path.1029.CrossRefPubMed
20.
Zurück zum Zitat Leek RD, Talks KL, Pezzella F, Turley H, Campo L, Brown NS, Bicknell R, Taylor M, Gatter KC, Harris AL: Relation of hypoxia-inducible factor-2α (HIF-2α) expression in tumor-infiltrative macrophages to tumor angiogenesis and the oxidative thymidine phosphorylase pathway in human breast cancer. Cancer Res. 2002, 62: 1326-1329.PubMed Leek RD, Talks KL, Pezzella F, Turley H, Campo L, Brown NS, Bicknell R, Taylor M, Gatter KC, Harris AL: Relation of hypoxia-inducible factor-2α (HIF-2α) expression in tumor-infiltrative macrophages to tumor angiogenesis and the oxidative thymidine phosphorylase pathway in human breast cancer. Cancer Res. 2002, 62: 1326-1329.PubMed
21.
Zurück zum Zitat Elbarghati L, Murdoch C, Lewis CE: Expression of hypoxia-inducible transcription factors by human macrophages: involvement of HIF-1 in the hypoxic induction of VEGF and mmP-7. J Leukoc Biol. 2005, 19-79. Suppl Elbarghati L, Murdoch C, Lewis CE: Expression of hypoxia-inducible transcription factors by human macrophages: involvement of HIF-1 in the hypoxic induction of VEGF and mmP-7. J Leukoc Biol. 2005, 19-79. Suppl
22.
Zurück zum Zitat Oda T, Hirota K, Nishi K, Takabuchi S, Oda S, Yamada H, Arai T, Fukuda K, Kita T, Adachi T, et al: Activation of hypoxia-inducible factor 1 during macrophage differentiation. Am J Physiol Cell Physiol. 2006, 291: C104-C113. 10.1152/ajpcell.00614.2005.CrossRefPubMed Oda T, Hirota K, Nishi K, Takabuchi S, Oda S, Yamada H, Arai T, Fukuda K, Kita T, Adachi T, et al: Activation of hypoxia-inducible factor 1 during macrophage differentiation. Am J Physiol Cell Physiol. 2006, 291: C104-C113. 10.1152/ajpcell.00614.2005.CrossRefPubMed
23.
Zurück zum Zitat Konur A, Kreutz M, Knuchel R, Krause SW, Andreesen R: Three-dimensional co-culture of human monocytes and macrophages with tumor cells: analysis of macrophage differentiation and activation. Int J Cancer. 1996, 66: 645-652. 10.1002/(SICI)1097-0215(19960529)66:5<645::AID-IJC11>3.0.CO;2-3.CrossRefPubMed Konur A, Kreutz M, Knuchel R, Krause SW, Andreesen R: Three-dimensional co-culture of human monocytes and macrophages with tumor cells: analysis of macrophage differentiation and activation. Int J Cancer. 1996, 66: 645-652. 10.1002/(SICI)1097-0215(19960529)66:5<645::AID-IJC11>3.0.CO;2-3.CrossRefPubMed
24.
Zurück zum Zitat Tait CR, Jones PF: Angiopoietins in tumours: the angiogenic switch. J Pathol. 2004, 204: 1-10. 10.1002/path.1618.CrossRefPubMed Tait CR, Jones PF: Angiopoietins in tumours: the angiogenic switch. J Pathol. 2004, 204: 1-10. 10.1002/path.1618.CrossRefPubMed
25.
Zurück zum Zitat Tsutsui S, Inoue H, Yasuda K, Suzuki K, Takeuchi H, Nishizaki T, Higashi H, Era S, Mori M: Angiopoietin 2 expression in invasive ductal carcinoma of the breast: its relationship to the VEGF expression and microvessel density. Breast Cancer Res Treat. 2006, 98: 261-266. 10.1007/s10549-005-9157-9.CrossRefPubMed Tsutsui S, Inoue H, Yasuda K, Suzuki K, Takeuchi H, Nishizaki T, Higashi H, Era S, Mori M: Angiopoietin 2 expression in invasive ductal carcinoma of the breast: its relationship to the VEGF expression and microvessel density. Breast Cancer Res Treat. 2006, 98: 261-266. 10.1007/s10549-005-9157-9.CrossRefPubMed
26.
Zurück zum Zitat Kuliszewska K, Maisonpierre PC, Jones N, Campbell AI, Master Z, Bendeck MP, Alitalo K, Dumont DJ, Yancopoulos GD, Stewart DJ: Biological action of angiopoietin-2 in a fibrin matrix model of angiogenesis is associated with activation of Tie2. Cardiovasc Res. 2001, 49: 659-670. 10.1016/S0008-6363(00)00231-5.CrossRef Kuliszewska K, Maisonpierre PC, Jones N, Campbell AI, Master Z, Bendeck MP, Alitalo K, Dumont DJ, Yancopoulos GD, Stewart DJ: Biological action of angiopoietin-2 in a fibrin matrix model of angiogenesis is associated with activation of Tie2. Cardiovasc Res. 2001, 49: 659-670. 10.1016/S0008-6363(00)00231-5.CrossRef
27.
Zurück zum Zitat De Palma M, Venneri MA, Galli R, Sergi Sergi L, Politi LS, Sampaolesi M, Naldini L: Tie2 identifies a hematopoietic lineage of proangiogenic monocytes required for tumor vessel formation and a mesenchymal population of pericyte progenitors. Cancer Cell. 2005, 8: 211-226. 10.1016/j.ccr.2005.08.002.CrossRefPubMed De Palma M, Venneri MA, Galli R, Sergi Sergi L, Politi LS, Sampaolesi M, Naldini L: Tie2 identifies a hematopoietic lineage of proangiogenic monocytes required for tumor vessel formation and a mesenchymal population of pericyte progenitors. Cancer Cell. 2005, 8: 211-226. 10.1016/j.ccr.2005.08.002.CrossRefPubMed
28.
Zurück zum Zitat Venneri MA, De Palma M, Ponzoni M, Pucci F, Scielzo C, Zonari E, Mazzieri R, Doglioni C, Naldini L: Identification of pro-angiogenic TIE2-expressing monocytes (TEMs) in human peripheral blood and cancer. Blood. Venneri MA, De Palma M, Ponzoni M, Pucci F, Scielzo C, Zonari E, Mazzieri R, Doglioni C, Naldini L: Identification of pro-angiogenic TIE2-expressing monocytes (TEMs) in human peripheral blood and cancer. Blood.
29.
Zurück zum Zitat Murdoch C, Tazzyman S, Webster S, Lewis CE: Expression of Tie-2 by human monocytes and their responses to angiopoietin-2. J Immunol. 2007, 178: 7405-7411.CrossRefPubMed Murdoch C, Tazzyman S, Webster S, Lewis CE: Expression of Tie-2 by human monocytes and their responses to angiopoietin-2. J Immunol. 2007, 178: 7405-7411.CrossRefPubMed
30.
Zurück zum Zitat Krikun G, F Schatz T, Finlay S, Kadner A, Mesia R, Gerrets H, Lockwood CJ: Expression of angiopoietin-2 by human endometrial endothelial cells: regulation by hypoxia and inflammation. Biochem Biophys Res Commun. 2000, 275: 159-163. 10.1006/bbrc.2000.3277.CrossRefPubMed Krikun G, F Schatz T, Finlay S, Kadner A, Mesia R, Gerrets H, Lockwood CJ: Expression of angiopoietin-2 by human endometrial endothelial cells: regulation by hypoxia and inflammation. Biochem Biophys Res Commun. 2000, 275: 159-163. 10.1006/bbrc.2000.3277.CrossRefPubMed
31.
Zurück zum Zitat Balkwill FR: Tumour necrosis factor and cancer. Prog Growth Factor Res. 1992, 4: 121-137. 10.1016/0955-2235(92)90027-F.CrossRefPubMed Balkwill FR: Tumour necrosis factor and cancer. Prog Growth Factor Res. 1992, 4: 121-137. 10.1016/0955-2235(92)90027-F.CrossRefPubMed
32.
Zurück zum Zitat Kim I, Kim JH, Ryu YS, Liu M, Koh GY: Tumor necrosis factor-α up-regulates angiopoietin-2 in human umbilical vein endothelial cells. Biochem Biophys Res Commun. 2000, 269: 361-365. 10.1006/bbrc.2000.2296.CrossRefPubMed Kim I, Kim JH, Ryu YS, Liu M, Koh GY: Tumor necrosis factor-α up-regulates angiopoietin-2 in human umbilical vein endothelial cells. Biochem Biophys Res Commun. 2000, 269: 361-365. 10.1006/bbrc.2000.2296.CrossRefPubMed
Metadaten
Titel
Inflammation and breast cancer. Microenvironmental factors regulating macrophage function in breast tumours: hypoxia and angiopoietin-2
verfasst von
Claire E Lewis
Russell Hughes
Publikationsdatum
01.06.2007
Verlag
BioMed Central
Erschienen in
Breast Cancer Research / Ausgabe 3/2007
Elektronische ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr1679

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