Role of Myeloid Cells in Tumor Angiogenesis

Chapter
First Online:
Part of the Milestones in Drug Therapy book series (MDT)

Abstract

Angiogenesis is a fundamental process in embryonic and adult life and is also important for tissue repair [1, 2]. Normal microvessels are organized as highly ordered structures consisting of endothelial cells, pericytes, and basement membrane. Pericytes are required for vascular stabilization through establishment of contact with endothelial cells along the length of the vessels and also through paracrine signaling [3]. Angiogenesis is a relatively rare event in the adult, except in particular circumstances such as the cyclical growth of vessels in the ovarian corpus luteum [4] or during pregnancy [23].

Keywords

Vascular Endothelial Growth Factor Myeloid Cell Vascular Endothelial Growth Factor Family Placenta Growth Factor Leukemoid Reaction 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.

References

  1. 1.
    Red-Horse K, Crawford Y, Shojaei F, Ferrara N (2007) Endothelium-microenvironment interactions in the developing embryo and in the adult. Dev Cell 12:181–194PubMedCrossRefGoogle Scholar
  2. 2.
    Chung AS, Lee J, Ferrara N (2010) Targeting the tumour vasculature: insights from physiological angiogenesis. Nat Rev 10:505–514CrossRefGoogle Scholar
  3. 3.
    Hirschi KK, D’Amore PA (1996) Pericytes in the microvasculature. Cardiovasc Res 32:687–698PubMedGoogle Scholar
  4. 4.
    Ferrara N, Chen H, Davis-Smyth T et al (1998) Vascular endothelial growth factor is essential for corpus luteum angiogenesis. Nat Med 4:336–340PubMedCrossRefGoogle Scholar
  5. 5.
    Ferrara N, Mass RD, Campa C, Kim R (2007) Targeting VEGF-A to treat cancer and age-related macular degeneration. Annu Rev Med 58:491–504PubMedCrossRefGoogle Scholar
  6. 6.
    Kerbel RS (2008) Tumor angiogenesis. N Engl J Med 358:2039–2049PubMedCrossRefGoogle Scholar
  7. 7.
    Ferrara N, Kerbel RS (2005) Angiogenesis as a therapeutic target. Nature 438:967–974PubMedCrossRefGoogle Scholar
  8. 8.
    Crawford Y, Ferrara N (2008) VEGF inhibition: insights from preclinical and clinical studies. Cell Tissue Res 335:261–269PubMedCrossRefGoogle Scholar
  9. 9.
    Ferrara N (2010) Vascular endothelial growth factor and age-related macular degeneration: from basic science to therapy. Nat Med 16:1107–1111PubMedCrossRefGoogle Scholar
  10. 10.
    Ferrara N, Carver Moore K, Chen H et al (1996) Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 380:439–442PubMedCrossRefGoogle Scholar
  11. 11.
    Ferrara N, Gerber HP, LeCouter J (2003) The biology of VEGF and its receptors. Nat Med 9:669–676PubMedCrossRefGoogle Scholar
  12. 12.
    Kim KJ, Li B, Winer J et al (1993) Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumor growth in vivo. Nature 362:841–844PubMedCrossRefGoogle Scholar
  13. 13.
    Ellis LM, Hicklin DJ (2008) VEGF-targeted therapy: mechanisms of anti-tumour activity. Nat Rev 8:579–591CrossRefGoogle Scholar
  14. 14.
    Ferrara N (2004) Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev 25:581–611PubMedCrossRefGoogle Scholar
  15. 15.
    Alitalo K, Tammela T, Petrova TV (2005) Lymphangiogenesis in development and human disease. Nature 438:946–953PubMedCrossRefGoogle Scholar
  16. 16.
    Presta LG, Chen H, O’Connor SJ et al (1997) Humanization of an anti-VEGF monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res 57:4593–4599PubMedGoogle Scholar
  17. 17.
    Ferrara N, Hillan KJ, Gerber HP, Novotny W (2004) Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Discov 3:391–400PubMedCrossRefGoogle Scholar
  18. 18.
    Hurwitz H, Fehrenbacher L, Novotny W et al (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350:2335–2342PubMedCrossRefGoogle Scholar
  19. 19.
    Sandler A, Gray R, Perry MC et al (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355:2542–2550PubMedCrossRefGoogle Scholar
  20. 20.
    Escudier B, Pluzanska A, Koralewski P et al (2008) Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet 370:2103–2111CrossRefGoogle Scholar
  21. 21.
    Kowanetz M, Ferrara N (2006) Vascular endothelial growth factor signaling pathways: therapeutic perspective. Clin Cancer Res 12:5018–5022PubMedCrossRefGoogle Scholar
  22. 22.
    Shojaei F, Zhong C, Wu X, Yu L, Ferrara N (2008) Role of myeloid cells in tumor angiogenesis and growth. Trends Cell Biol 18:372–378PubMedCrossRefGoogle Scholar
  23. 23.
    Balkwill F, Mantovani A (2001) Inflammation and cancer: back to Virchow? Lancet 357:539–545PubMedCrossRefGoogle Scholar
  24. 24.
    Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420:860–867PubMedCrossRefGoogle Scholar
  25. 25.
    Lin WW, Karin M (2007) A cytokine-mediated link between innate immunity, inflammation, and cancer. J Clin Invest 117:1175–1183PubMedCrossRefGoogle Scholar
  26. 26.
    Joyce JA, Pollard JW (2009) Microenvironmental regulation of metastasis. Nat Rev 9:239–252CrossRefGoogle Scholar
  27. 27.
    Ahn GO, Brown JM (2008) Matrix metalloproteinase-9 is required for tumor vasculogenesis but not for angiogenesis: role of bone marrow-derived myelomonocytic cells. Cancer Cell 13:193–205PubMedCrossRefGoogle Scholar
  28. 28.
    Mantovani A, Romero P, Palucka AK, Marincola FM (2008) Tumour immunity: effector response to tumour and role of the microenvironment. Lancet 371:771–7783PubMedCrossRefGoogle Scholar
  29. 29.
    Pollard JW (2004) Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev 4:71–78CrossRefGoogle Scholar
  30. 30.
    Pollard JW (2009) Trophic macrophages in development and disease. Nat Rev Immunol 9:259–270PubMedCrossRefGoogle Scholar
  31. 31.
    Bingle L, Brown NJ, Lewis CE (2002) The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies. J Pathol 196:254–265PubMedCrossRefGoogle Scholar
  32. 32.
    Finak G, Bertos N, Pepin F et al (2008) Stromal gene expression predicts clinical outcome in breast cancer. Nat Med 14:518–527PubMedCrossRefGoogle Scholar
  33. 33.
    Solinas G, Germano G, Mantovani A, Allavena P (2009) Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation. J Leukoc Biol 86:1065–1073PubMedCrossRefGoogle Scholar
  34. 34.
    Murdoch C, Giannoudis A, Lewis CE (2004) Mechanisms regulating the recruitment of macrophages into hypoxic areas of tumors and other ischemic tissues. Blood 104:2224–2234PubMedCrossRefGoogle Scholar
  35. 35.
    Mantovani A, Sozzani S, Locati M, Allavena P, Sica A (2002) Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol 23:549–555PubMedCrossRefGoogle Scholar
  36. 36.
    Murdoch C, Muthana M, Coffelt SB, Lewis CE (2008) The role of myeloid cells in the promotion of tumour angiogenesis. Nat Rev 8:618–631CrossRefGoogle Scholar
  37. 37.
    De Palma M, Venneri MA, Galli R et al (2005) Tie2 identifies a hematopoietic lineage of proangiogenic monocytes required for tumor vessel formation and a mesenchymal population of pericyte progenitors. Cancer Cell 8:211–226PubMedCrossRefGoogle Scholar
  38. 38.
    De Palma M, Murdoch C, Venneri MA, Naldini L, Lewis CE (2007) Tie2-expressing monocytes: regulation of tumor angiogenesis and therapeutic implications. Trends Immunol 28:519–524PubMedCrossRefGoogle Scholar
  39. 39.
    Murdoch C, Tazzyman S, Webster S, Lewis CE (2007) Expression of Tie-2 by human monocytes and their responses to angiopoietin-2. J Immunol 178:7405–7411PubMedGoogle Scholar
  40. 40.
    De Palma M, Naldini L (2009) Tie2-expressing monocytes (TEMs): novel targets and vehicles of anticancer therapy? Biochim Biophys Acta 1796:5–10PubMedGoogle Scholar
  41. 41.
    Oliner J, Min H, Leal J et al (2004) Suppression of angiogenesis and tumor growth by selective inhibition of angiopoietin-2. Cancer cell 6:507–516PubMedCrossRefGoogle Scholar
  42. 42.
    Brown JL, Cao ZA, Pinzon-Ortiz M et al (2010) A human monoclonal anti-ANG2 antibody leads to broad antitumor activity in combination with VEGF inhibitors and chemotherapy agents in preclinical models. Mol Cancer Ther 9:145–156PubMedCrossRefGoogle Scholar
  43. 43.
    Coxon A, Bready J, Min H et al (2010) Context-dependent role of angiopoietin-1 inhibition in the suppression of angiogenesis and tumor growth: implications for AMG 386, an angiopoietin-1/2-neutralizing peptibody. Mol Cancer Ther 9:2641–2651PubMedCrossRefGoogle Scholar
  44. 44.
    Huang H, Bhat A, Woodnutt G, Lappe R (2010) Targeting the ANGPT-TIE2 pathway in malignancy. Nat Rev 10:575–585CrossRefGoogle Scholar
  45. 45.
    Tazzyman S, Lewis CE, Murdoch C (2009) Neutrophils: key mediators of tumour angiogenesis. Int J Exp Pathol 90:222–231PubMedCrossRefGoogle Scholar
  46. 46.
    Fridlender ZG, Sun J, Kim S et al (2009) Polarization of tumor-associated neutrophil phenotype by TGF-beta: “N1” versus “N2” TAN. Cancer Cell 16:183–194PubMedCrossRefGoogle Scholar
  47. 47.
    Crivellato E, Nico B, Ribatti D (2008) Mast cells and tumour angiogenesis: new insight from experimental carcinogenesis. Cancer Lett 269:1–6PubMedCrossRefGoogle Scholar
  48. 48.
    Yang L, DeBusk LM, Fukuda K et al (2004) Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis. Cancer Cell 6:409–421PubMedCrossRefGoogle Scholar
  49. 49.
    Talmadge JE (2007) Pathways mediating the expansion and immunosuppressive activity of myeloid-derived suppressor cells and their relevance to cancer therapy. Clin Cancer Res 13(18 Pt 1):5243–5248PubMedCrossRefGoogle Scholar
  50. 50.
    Marigo I, Dolcetti L, Serafini P, Zanovello P, Bronte V (2008) Tumor-induced tolerance and immune suppression by myeloid derived suppressor cells. Immunol Rev 222:162–179PubMedCrossRefGoogle Scholar
  51. 51.
    Gabrilovich DI, Nagaraj S (2009) Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 9:162–174PubMedCrossRefGoogle Scholar
  52. 52.
    Shojaei F, Wu X, Malik AK et al (2007) Tumor refractoriness to anti-VEGF treatment is mediated by CD11b+Gr1+ myeloid cells. Nat Biotechnol 25:911–920PubMedCrossRefGoogle Scholar
  53. 53.
    Barleon B, Sozzani S, Zhou D, Weich HA, Mantovani A, Marme D (1996) Migration of human monocytes in response to vascular endothelial growth factor (VEGF) is mediated via the VEGF receptor flt-1. Blood 87:3336–3343PubMedGoogle Scholar
  54. 54.
    Park JE, Chen HH, Winer J, Houck KA, Ferrara N (1994) Placenta growth factor. Potentiation of vascular endothelial growth factor bioactivity, in vitro and in vivo, and high affinity binding to Flt-1 but not to Flk-1/KDR. J Biol Chem 269:25646–25654PubMedGoogle Scholar
  55. 55.
    Olofsson B, Korpelainen E, Pepper MS et al (1998) Vascular endothelial growth factor B (VEGF-B) binds to VEGF receptor-1 and regulates plasminogen activator activity in endothelial cells. Proc Natl Acad Sci U S A 95:11709–11714PubMedCrossRefGoogle Scholar
  56. 56.
    Davis-Smyth T, Chen H, Park J, Presta LG, Ferrara N (1996) The second immunoglobulin-like domain of the VEGF tyrosine kinase receptor Flt-1 determines ligand binding and may initiate a signal transduction cascade. EMBO J 15:4919–4927PubMedGoogle Scholar
  57. 57.
    Fischer C, Jonckx B, Mazzone M et al (2007) Anti-PlGF inhibits growth of VEGF(R)-inhibitor-resistant tumors without affecting healthy vessels. Cell 131:463–475PubMedCrossRefGoogle Scholar
  58. 58.
    Bais C, Wu X, Yao J et al (2010) PlGF blockade does not inhibit angiogenesis during primary tumor growth. Cell 141:166–177PubMedCrossRefGoogle Scholar
  59. 59.
    Mollay C, Wechselberger C, Mignogna G et al (1999) Bv8, a small protein from frog skin and its homologue from snake venom induce hyperalgesia in rats. Eur J Pharmacol 374:189–196PubMedCrossRefGoogle Scholar
  60. 60.
    LeCouter J, Kowalski J, Foster J et al (2001) Identification of an angiogenic mitogen selective for endocrine gland endothelium. Nature 412:877–884PubMedCrossRefGoogle Scholar
  61. 61.
    Li M, Bullock CM, Knauer DJ, Ehlert FJ, Zhou QY (2001) Identification of two Prokineticin cDNAs: recombinant proteins potently contract gestrointestinal smooth muscle. Mol Pharmacol 59:692–698PubMedGoogle Scholar
  62. 62.
    Shojaei F, Wu X, Zhong C et al (2007) Bv8 regulates myeloid-cell-dependent tumour angiogenesis. Nature 450:825–831PubMedCrossRefGoogle Scholar
  63. 63.
    Metcalf D (1989) The molecular control of cell division, differentiation commitment and maturation in haemopoietic cells. Nature 339:27–30PubMedCrossRefGoogle Scholar
  64. 64.
    Christopher MJ, Link DC (2007) Regulation of neutrophil homeostasis. Curr Opin Hematol 14:3–8PubMedCrossRefGoogle Scholar
  65. 65.
    Shojaei F, Wu X, Qu X et al (2009) G-CSF-initiated myeloid cell mobilization and angiogenesis mediate tumor refractoriness to anti-VEGF therapy in mouse models. Proc Natl Acad Sci U S A 106:6742–6747PubMedCrossRefGoogle Scholar
  66. 66.
    Zhong C, Qu X, Tan M, Meng YG, Ferrara N (2009) Characterization and regulation of Bv8 in human blood cells. Clin Cancer Res 15:2675–2684PubMedCrossRefGoogle Scholar
  67. 67.
    Nguyen DX, Bos PD, Massague J (2009) Metastasis: from dissemination to organ-specific colonization. Nat Rev 9:274–284CrossRefGoogle Scholar
  68. 68.
    Psaila B, Lyden D (2009) The metastatic niche: adapting the foreign soil. Nat Rev 9:285–293CrossRefGoogle Scholar
  69. 69.
    Kaplan RN, Riba RD, Zacharoulis S et al (2005) VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 438:820–827PubMedCrossRefGoogle Scholar
  70. 70.
    Hiratsuka S, Watanabe A, Aburatani H, Maru Y (2006) Tumour-mediated upregulation of chemoattractants and recruitment of myeloid cells predetermines lung metastasis. Nat Cell Biol 8:1369–1375PubMedCrossRefGoogle Scholar
  71. 71.
    Kim S, Takahashi H, Lin WW et al (2009) Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis. Nature 457:102–106PubMedCrossRefGoogle Scholar
  72. 72.
    Erler JT, Bennewith KL, Cox TR et al (2009) Hypoxia-induced lysyl oxidase is a critical mediator of bone marrow cell recruitment to form the premetastatic niche. Cancer Cell 15:35–44PubMedCrossRefGoogle Scholar
  73. 73.
    Dawson MR, Duda DG, Fukumura D, Jain RK (2009) VEGFR1-activity-independent metastasis formation. Nature 461:E4PubMedCrossRefGoogle Scholar
  74. 74.
    Kowanetz M, Wu X, Lee J et al (2010) Granulocyte-colony stimulating factor promotes lung metastasis through mobilization of Ly6G+Ly6C+ granulocytes. Proc Acad Natl Sci U S A 107:21248–22155CrossRefGoogle Scholar
  75. 75.
    Hiratsuka S, Nakamura K, Iwai S et al (2002) MMP9 induction by vascular endothelial growth factor receptor-1 is involved in lung-specific metastasis. Cancer Cell 2:289–300PubMedCrossRefGoogle Scholar
  76. 76.
    Acuff HB, Carter KJ, Fingleton B, Gorden DL, Matrisian LM (2006) Matrix metalloproteinase-9 from bone marrow-derived cells contributes to survival but not growth of tumor cells in the lung microenvironment. Cancer Res 66:259–266PubMedCrossRefGoogle Scholar
  77. 77.
    Ryckman C, McColl SR, Vandal K et al (2003) Role of S100A8 and S100A9 in neutrophil recruitment in response to monosodium urate monohydrate crystals in the air-pouch model of acute gouty arthritis. Arthritis Rheum 48:2310–2320PubMedCrossRefGoogle Scholar
  78. 78.
    Vandal K, Rouleau P, Boivin A, Ryckman C, Talbot M, Tessier PA (2003) Blockade of S100A8 and S100A9 suppresses neutrophil migration in response to lipopolysaccharide. J Immunol 171:2602–2609PubMedGoogle Scholar
  79. 79.
    Crawford J, Ozer H, Stoller R et al (1991) Reduction by granulocyte colony-stimulating factor of fever and neutropenia induced by chemotherapy in patients with small-cell lung cancer. N Engl J Med 325:164–170PubMedCrossRefGoogle Scholar
  80. 80.
    Hirasawa K, Kitamura T, Oka T, Matsushita H (2002) Bladder tumor producing granulocyte colony-stimulating factor and parathyroid hormone related protein. J Urol 167:2130PubMedCrossRefGoogle Scholar
  81. 81.
    Hasegawa S, Suda T, Negi K, Hattori Y (2007) Lung large cell carcinoma producing granulocyte-colony-stimulating factor. Ann Thorac Surg 83:308–310PubMedCrossRefGoogle Scholar
  82. 82.
    Yamamoto S, Takashima S, Ogawa H et al (1999) Granulocyte-colony-stimulating-factor-producing hepatocellular carcinoma. J Gastroenterol 34:640–644PubMedCrossRefGoogle Scholar
  83. 83.
    Mabuchi S, Matsumoto Y, Morii E, Morishige K, Kimura T (2010) The first 2 cases of granulocyte colony-stimulating factor producing adenocarcinoma of the uterine cervix. Int J Gynecol Pathol 29:483–487PubMedCrossRefGoogle Scholar
  84. 84.
    Granger JM, Kontoyiannis DP (2009) Etiology and outcome of extreme leukocytosis in 758 nonhematologic cancer patients: a retrospective, single-institution study. Cancer 115:3919–3923PubMedCrossRefGoogle Scholar
  85. 85.
    Perez FA, Fligner CL, Yu EY (2009) Rapid clinical deterioration and leukemoid reaction after treatment of urothelial carcinoma of the bladder: possible effect of granulocyte colony-stimulating factor. J Clin Oncol 27:215–217CrossRefGoogle Scholar
  86. 86.
    Hamilton JA (2008) Colony-stimulating factors in inflammation and autoimmunity. Nat Rev Immunol 8:533–544PubMedCrossRefGoogle Scholar
  87. 87.
    Liu BY, Soloviev I, Chang P et al (2010) Stromal cell-derived factor-1/CXCL12 contributes to MMTV-Wnt1 tumor growth involving Gr1+CD11b+ cells. PLoS One 5:e8611PubMedCrossRefGoogle Scholar
  88. 88.
    Patel S, Player MR (2009) Colony-stimulating factor-1 receptor inhibitors for the treatment of cancer and inflammatory disease. Curr Top Med Chem 9:599–610PubMedCrossRefGoogle Scholar
  89. 89.
    Stanley ER, Berg KL, Einstein DB et al (1997) Biology and action of colony-stimulating factor-1. Mol Reprod Dev 46:4–10PubMedCrossRefGoogle Scholar
  90. 90.
    Sherr CJ, Rettenmier CW, Sacca R, Roussel MF, Look AT, Stanley ER (1985) The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF-1. Cell 41:665–676PubMedCrossRefGoogle Scholar
  91. 91.
    Aharinejad S, Paulus P, Sioud M et al (2004) Colony-stimulating factor-1 blockade by antisense oligonucleotides and small interfering RNAs suppresses growth of human mammary tumor xenografts in mice. Cancer Res 64:5378–5384PubMedCrossRefGoogle Scholar
  92. 92.
    Paulus P, Stanley ER, Schafer R, Abraham D, Aharinejad S (2006) Colony-stimulating factor-1 antibody reverses chemoresistance in human MCF-7 breast cancer xenografts. Cancer Res 66:4349–4356PubMedCrossRefGoogle Scholar
  93. 93.
    Kubota Y, Takubo K, Shimizu T et al (2009) M-CSF inhibition selectively targets pathological angiogenesis and lymphangiogenesis. J Exp Med 206:1089–1102PubMedCrossRefGoogle Scholar
  94. 94.
    Murray LJ, Abrams TJ, Long KR et al (2003) SU11248 inhibits tumor growth and CSF-1R-dependent osteolysis in an experimental breast cancer bone metastasis model. Clin Exp Metastasis 20:757–766PubMedCrossRefGoogle Scholar
  95. 95.
    Guo J, Marcotte PA, McCall JO et al (2006) Inhibition of phosphorylation of the colony-stimulating factor-1 receptor (c-Fms) tyrosine kinase in transfected cells by ABT-869 and other tyrosine kinase inhibitors. Mol Cancer Ther 5:1007–1013PubMedCrossRefGoogle Scholar
  96. 96.
    Sonpavde G, Hutson TE, Rini BI (2008) Axitinib for renal cell carcinoma. Expert Opin Investig Drugs 17:741–748PubMedCrossRefGoogle Scholar
  97. 97.
    Kalluri R, Zeisberg M (2006) Fibroblasts in cancer. Nat Rev 6:392–401CrossRefGoogle Scholar
  98. 98.
    Bhowmick NA, Neilson EG, Moses HL (2004) Stromal fibroblasts in cancer initiation and progression. Nature 432:332–337PubMedCrossRefGoogle Scholar
  99. 99.
    Crawford Y, Kasman I, Yu L et al (2009) PDGF-C mediates the angiogenic and tumorigenic properties of fibroblasts associated with tumors refractory to anti-VEGF treatment. Cancer Cell 15:21–34PubMedCrossRefGoogle Scholar

Copyright information

© Springer Basel AG 2012

Authors and Affiliations

  1. 1.Genentech Inc.South San FranciscoUSA

Personalised recommendations