The Role of the Tumor Microenvironment in Regulating Angiogenesis

Chapter

Abstract

The tumor microenvironment plays a crucial role in cancer development and progression. Paracrine signaling between tumor cells and the nonneoplastic, genetically normal, cells that make up the microenvironment is a critical component influencing the progression of tumors from the in situ stage to metastatic disease. Despite the importance of these paracrine signaling mechanisms and factors, the vast majority of academic research and development in the pharmaceutical industry is still targeted toward mutations and aberrant signaling pathways within tumor cells. As a result, the intercellular signaling between tumor cells and the microenvironment has not been as extensively studied with regard to the regulation of angiogenesis. In this chapter we define the key players in the regulation of angiogenesis and examine how their expression is regulated in the microenvironment. The resulting analysis presents observations that at first glance may seem paradoxical. However, these nuances serve to underscore the complexity of interactions and the need to better delineate and define the environmental context underlying these mechanisms.

Keywords

Microenvironment Angiogenesis Cancer 

References

  1. 1.
    Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74.PubMedCrossRefGoogle Scholar
  2. 2.
    Ronnov-Jessen L, Petersen OW, Bissell MJ. Cellular changes involved in conversion of normal to malignant breast: importance of the stromal reaction. Physiol Rev. 1996;76(1):69–125.PubMedCrossRefGoogle Scholar
  3. 3.
    Chung LW, Davies R. Prostate epithelial differentiation is dictated by its surrounding stroma. Mol Biol Rep. 1996;23(1):13–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Tuxhorn JA, Ayala GE, Rowley DR. Reactive stroma in prostate cancer progression. J Urol. 2001;166(6):2472–83.PubMedCrossRefGoogle Scholar
  5. 5.
    Henshall SM, et al. Altered expression of androgen receptor in the malignant epithelium and adjacent stroma is associated with early relapse in prostate cancer. Cancer Res. 2001;61(2):423–7.PubMedGoogle Scholar
  6. 6.
    Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell. 1996;86(3):353–64.PubMedCrossRefGoogle Scholar
  7. 7.
    Camps JL, et al. Fibroblast-mediated acceleration of human epithelial tumor growth in vivo. Proc Natl Acad Sci U S A. 1990;87(1):75–9.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Grey AM, et al. Purification of the migration stimulating factor produced by fetal and breast cancer patient fibroblasts. Proc Natl Acad Sci U S A. 1989;86(7):2438–42.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Picard O, Rolland Y, Poupon MF. Fibroblast-dependent tumorigenicity of cells in nude mice: implication for implantation of metastases. Cancer Res. 1986;46(7):3290–4.PubMedGoogle Scholar
  10. 10.
    Olumi AF, et al. Carcinoma-associated fibroblasts direct tumor progression of initiated human prostatic epithelium. Cancer Res. 1999;59(19):5002–11.PubMedGoogle Scholar
  11. 11.
    Hom YK, et al. Uterine and vaginal organ growth requires epidermal growth factor receptor signaling from stroma. Endocrinology. 1998;139(3):913–21.PubMedCrossRefGoogle Scholar
  12. 12.
    Donjacour AA, Cunha GR. Stromal regulation of epithelial function. Cancer Treat Res. 1991;53:335–64.PubMedCrossRefGoogle Scholar
  13. 13.
    Cunha GR, et al. Stromal-epithelial interactions in adult organs. Cell Differ. 1985;17(3):137–48.PubMedCrossRefGoogle Scholar
  14. 14.
    Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med. 1971;285(21):1182–6.PubMedCrossRefGoogle Scholar
  15. 15.
    Akiyama H, et al. Induction of VEGF gene expression by retinoic acid through Sp1-binding sites in retinoblastoma Y79 cells. Invest Ophthalmol Vis Sci. 2002;43(5):1367–74.PubMedGoogle Scholar
  16. 16.
    Damert A, Ikeda E, Risau W. Activator-protein-1 binding potentiates the hypoxia-induciblefactor-1-mediated hypoxia-induced transcriptional activation of vascular-endothelial growth factor expression in C6 glioma cells. Biochem J. 1997;327(Pt 2):419–23.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Rak J, et al. Mutant ras oncogenes upregulate VEGF/VPF expression: implications for induction and inhibition of tumor angiogenesis. Cancer Res. 1995;55(20):4575–80.PubMedGoogle Scholar
  18. 18.
    Wojta J, et al. Hepatocyte growth factor increases expression of vascular endothelial growth factor and plasminogen activator inhibitor-1 in human keratinocytes and the vascular endothelial growth factor receptor flk-1 in human endothelial cells. Lab Investig. 1999;79(4):427–38.PubMedGoogle Scholar
  19. 19.
    Xiong S, et al. Up-regulation of vascular endothelial growth factor in breast cancer cells by the heregulin-beta1-activated p38 signaling pathway enhances endothelial cell migration. Cancer Res. 2001;61(4):1727–32.PubMedGoogle Scholar
  20. 20.
    Watnick R, et al. Ras modulates Myc activity to repress thrombospondin-1 expression and increase tumor angiogenesis. Cancer Cell. 2003;3(3):219–31.PubMedCrossRefGoogle Scholar
  21. 21.
    Rak J, et al. Oncogenes and tumor angiogenesis: differential modes of vascular endothelial growth factor up-regulation in ras-transformed epithelial cells and fibroblasts. Cancer Res. 2000;60(2):490–8.PubMedGoogle Scholar
  22. 22.
    Chambers AF, Groom AC, MacDonald IC. Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer. 2002;2(8):563–72.PubMedCrossRefGoogle Scholar
  23. 23.
    Pettaway CA, et al. Selection of highly metastatic variants of different human prostatic carcinomas using orthotopic implantation in nude mice. Clin Cancer Res. 1996;2(9):1627–36.PubMedGoogle Scholar
  24. 24.
    Leung DW, et al. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science. 1989;246(4935):1306–9.PubMedCrossRefGoogle Scholar
  25. 25.
    Senger DR, et al. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science. 1983;219(4587):983–5.PubMedCrossRefGoogle Scholar
  26. 26.
    Brogi E, et al. Indirect angiogenic cytokines upregulate VEGF and bFGF gene expression in vascular smooth muscle cells, whereas hypoxia upregulates VEGF expression only. Circulation. 1994;90(2):649–52.PubMedCrossRefGoogle Scholar
  27. 27.
    Tsai JC, Goldman CK, Gillespie GY. Vascular endothelial growth factor in human glioma cell lines: induced secretion by EGF, PDGF-BB, and bFGF. J Neurosurg. 1995;82(5):864–73.PubMedCrossRefGoogle Scholar
  28. 28.
    Fukumura D, et al. Tumor induction of VEGF promoter activity in stromal cells. Cell. 1998;94(6):715–25.PubMedCrossRefGoogle Scholar
  29. 29.
    Kim KJ, et al. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature. 1993;362(6423):841–4.PubMedCrossRefGoogle Scholar
  30. 30.
    Gerber HP, et al. Complete inhibition of rhabdomyosarcoma xenograft growth and neovascularization requires blockade of both tumor and host vascular endothelial growth factor. Cancer Res. 2000;60(22):6253–8.PubMedGoogle Scholar
  31. 31.
    Folkman J, Klagsbrun M. Angiogenic factors. Science. 1987;235(4787):442–7.PubMedCrossRefGoogle Scholar
  32. 32.
    Shing Y, et al. Heparin affinity: purification of a tumor-derived capillary endothelial cell growth factor. Science. 1984;223(4642):1296–9.PubMedCrossRefGoogle Scholar
  33. 33.
    Klagsbrun M, et al. Human tumor cells synthesize an endothelial cell growth factor that is structurally related to basic fibroblast growth factor. Proc Natl Acad Sci U S A. 1986;83(8):2448–52.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Dionne CA, et al. Cloning and expression of two distinct high-affinity receptors cross-reacting with acidic and basic fibroblast growth factors. EMBO J. 1990;9(9):2685–92.PubMedPubMedCentralGoogle Scholar
  35. 35.
    Abraham JA, et al. Human basic fibroblast growth factor: nucleotide sequence and genomic organization. EMBO J. 1986;5(10):2523–8.PubMedPubMedCentralGoogle Scholar
  36. 36.
    Abraham JA, et al. Nucleotide sequence of a bovine clone encoding the angiogenic protein, basic fibroblast growth factor. Science. 1986;233(4763):545–8.PubMedCrossRefGoogle Scholar
  37. 37.
    Rogelj S, et al. Characterization of tumors produced by signal peptide-basic fibroblast growth factor-transformed cells. J Cell Biochem. 1989;39(1):13–23.PubMedCrossRefGoogle Scholar
  38. 38.
    Rogelj S, et al. Basic fibroblast growth factor fused to a signal peptide transforms cells. Nature. 1988;331(6152):173–5.PubMedCrossRefGoogle Scholar
  39. 39.
    Gleave M, et al. Acceleration of human prostate cancer growth in vivo by factors produced by prostate and bone fibroblasts. Cancer Res. 1991;51(14):3753–61.PubMedGoogle Scholar
  40. 40.
    Guddo F, et al. The expression of basic fibroblast growth factor (bFGF) in tumor-associated stromal cells and vessels is inversely correlated with non-small cell lung cancer progression. Hum Pathol. 1999;30(7):788–94.PubMedCrossRefGoogle Scholar
  41. 41.
    Qu Z, et al. Synthesis of basic fibroblast growth factor by murine mast cells. Regulation by transforming growth factor beta, tumor necrosis factor alpha, and stem cell factor. Int Arch Allergy Immunol. 1998;115(1):47–54.PubMedCrossRefGoogle Scholar
  42. 42.
    Roberts AB, et al. Transforming growth factor type beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci U S A. 1986;83(12):4167–71.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Baird A, Durkin T. Inhibition of endothelial cell proliferation by type beta-transforming growth factor: interactions with acidic and basic fibroblast growth factors. Biochem Biophys Res Commun. 1986;138(1):476–82.PubMedCrossRefGoogle Scholar
  44. 44.
    Frater-Schroder M, et al. Transforming growth factor-beta inhibits endothelial cell proliferation. Biochem Biophys Res Commun. 1986;137(1):295–302.PubMedCrossRefGoogle Scholar
  45. 45.
    Pertovaara L, et al. Vascular endothelial growth factor is induced in response to transforming growth factor-beta in fibroblastic and epithelial cells. J Biol Chem. 1994;269(9):6271–4.PubMedGoogle Scholar
  46. 46.
    Goldsmith KT, Gammon RB, Garver RI Jr. Modulation of bFGF in lung fibroblasts by TGF-beta and PDGF. Am J Phys. 1991;261(6 Pt 1):L378–85.Google Scholar
  47. 47.
    Murphy-Ullrich JE, Schultz-Cherry S, Hook M. Transforming growth factor-beta complexes with thrombospondin. Mol Biol Cell. 1992;3(2):181–8.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Penttinen RP, Kobayashi S, Bornstein P. Transforming growth factor beta increases mRNA for matrix proteins both in the presence and in the absence of changes in mRNA stability. Proc Natl Acad Sci U S A. 1988;85(4):1105–8.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Schultz-Cherry S, Lawler J, Murphy-Ullrich JE. The type 1 repeats of thrombospondin 1 activate latent transforming growth factor-beta. J Biol Chem. 1994;269(43):26783–8.PubMedGoogle Scholar
  50. 50.
    Schultz_Cherry S, Murphy_Ullrich JE. Thrombospondin causes activation of latent transforming growth factor-beta secreted by endothelial cells by a novel mechanism. J Cell Biol. 1993;122(4):923–32.PubMedCrossRefGoogle Scholar
  51. 51.
    Schultz_Cherry S, et al. Thrombospondin binds and activates the small and large forms of latent transforming growth factor-beta in a chemically defined system. J Biol Chem. 1994;269(43):26775–82.PubMedGoogle Scholar
  52. 52.
    Falanga V, et al. Hypoxia upregulates the synthesis of TGF-beta 1 by human dermal fibroblasts. J Invest Dermatol. 1991;97(4):634–7.PubMedCrossRefGoogle Scholar
  53. 53.
    Dong J, et al. VEGF-null cells require PDGFR alpha signaling-mediated stromal fibroblast recruitment for tumorigenesis. EMBO J. 2004;23(14):2800–10.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Majack RA, Mildbrandt J, Dixit VM. Induction of thrombospondin messenger RNA levels occurs as an immediate primary response to platelet-derived growth factor. J Biol Chem. 1987;262(18):8821–5.PubMedGoogle Scholar
  55. 55.
    Majack RA, Cook SC, Bornstein P. Platelet-derived growth factor and heparin-like glycosaminoglycans regulate thrombospondin synthesis and deposition in the matrix by smooth muscle cells. J Cell Biol. 1985;101(3):1059–70.PubMedCrossRefGoogle Scholar
  56. 56.
    Chang HJ, et al. Extracellular signal-regulated kinases and AP-1 mediate the up-regulation of vascular endothelial growth factor by PDGF in human vascular smooth muscle cells. Int J Oncol. 2006;28(1):135–41.PubMedGoogle Scholar
  57. 57.
    Sengupta K, et al. Thombospondin-1 disrupts estrogen-induced endothelial cell proliferation and migration and its expression is suppressed by estradiol. Mol Cancer Res. 2004;2(3):150–8.PubMedGoogle Scholar
  58. 58.
    Colombel M, et al. Androgens repress the expression of the angiogenesis inhibitor thrombospondin-1 in normal and neoplastic prostate. Cancer Res. 2005;65(1):300–8.PubMedGoogle Scholar
  59. 59.
    Gupta PB, et al. Systemic stromal effects of estrogen promote the growth of estrogen receptor-negative cancers. Cancer Res. 2007;67(5):2062–71.PubMedCrossRefGoogle Scholar
  60. 60.
    Kaipainen A, et al. PPARalpha deficiency in inflammatory cells suppresses tumor growth. PLoS One. 2007;2(2):e260.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Panigrahy D, et al. PPARalpha agonist fenofibrate suppresses tumor growth through direct and indirect angiogenesis inhibition. Proc Natl Acad Sci U S A. 2008;105(3):985–90.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Han J, et al. Transforming growth factor-beta1 (TGF-beta1) and TGF-beta2 decrease expression of CD36, the type B scavenger receptor, through mitogen-activated protein kinase phosphorylation of peroxisome proliferator-activated receptor-gamma. J Biol Chem. 2000;275(2):1241–6.PubMedCrossRefGoogle Scholar
  63. 63.
    Aljada A, et al. PPAR gamma ligands, rosiglitazone and pioglitazone, inhibit bFGF- and VEGF-mediated angiogenesis. Angiogenesis. 2008;11(4):361–7.PubMedCrossRefGoogle Scholar
  64. 64.
    Noel A, et al. Enhancement of tumorigenicity of human breast adenocarcinoma cells in nude mice by matrigel and fibroblasts. Br J Cancer. 1993;68(5):909–15.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Noel A, et al. Inhibition of stromal matrix metalloproteases: effects on breast-tumor promotion by fibroblasts. Int J Cancer. 1998;76(2):267–73.PubMedCrossRefGoogle Scholar
  66. 66.
    Bergers G, et al. Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat Cell Biol. 2000;2(10):737–44.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Yu Q, Stamenkovic I. Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis. Genes Dev. 2000;14(2):163–76.PubMedPubMedCentralGoogle Scholar
  68. 68.
    Dawson DW, et al. CD36 mediates the in vitro inhibitory effects of thrombospondin-1 on endothelial cells. J Cell Biol. 1997;138(3):707–17.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Saumet A, et al. Type 3 repeat/C-terminal domain of thrombospondin-1 triggers caspase-independent cell death through CD47/alphavbeta3 in promyelocytic leukemia NB4 cells. Blood. 2005;106(2):658–67.PubMedCrossRefGoogle Scholar
  70. 70.
    Lamy L, et al. Interactions between CD47 and thrombospondin reduce inflammation. J Immunol. 2007;178(9):5930–9.PubMedCrossRefGoogle Scholar
  71. 71.
    Henkin J, Volpert OV. Therapies using anti-angiogenic peptide mimetics of thrombospondin-1. Expert Opin Ther Targets. 2011;15(12):1369–86.PubMedCrossRefGoogle Scholar
  72. 72.
    Rodriguez_Manzaneque JC, et al. Thrombospondin-1 suppresses spontaneous tumor growth and inhibits activation of matrix metalloproteinase-9 and mobilization of vascular endothelial growth factor. Proc Natl Acad Sci U S A. 2001;98(22):12485–90.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Watnick RS, et al. Thrombospondin-1 repression is mediated via distinct mechanisms in fibroblasts and epithelial cells. Oncogene. 2015;34(22):2823–35.PubMedCrossRefGoogle Scholar
  74. 74.
    Li W, et al. GRK3 is essential for metastatic cells and promotes prostate tumor progression. Proc Natl Acad Sci U S A. 2014;111(4):1521–6.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Brown LF, et al. Vascular stroma formation in carcinoma in situ, invasive carcinoma, and metastatic carcinoma of the breast. Clin Cancer Res. 1999;5(5):1041–56.PubMedGoogle Scholar
  76. 76.
    Mueller MM, Fusenig NE. Tumor-stroma interactions directing phenotype and progression of epithelial skin tumor cells. Differentiation. 2002;70(9–10):486–97.PubMedCrossRefGoogle Scholar
  77. 77.
    Streit M, et al. Overexpression of thrombospondin-1 decreases angiogenesis and inhibits the growth of human cutaneous squamous cell carcinomas. Am J Pathol. 1999;155(2):441–52.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Wong SY, Purdie AT, Han P. Thrombospondin and other possible related matrix proteins in malignant and benign breast disease. An immunohistochemical study. Am J Pathol. 1992;140(6):1473–82.PubMedPubMedCentralGoogle Scholar
  79. 79.
    Bertin N, et al. Thrombospondin-1 and -2 messenger RNA expression in normal, benign, and neoplastic human breast tissues: correlation with prognostic factors, tumor angiogenesis, and fibroblastic desmoplasia. Cancer Res. 1997;57(3):396–9.PubMedGoogle Scholar
  80. 80.
    Clezardin P, et al. Expression of thrombospondin (TSP1) and its receptors (CD36 and CD51) in normal, hyperplastic, and neoplastic human breast. Cancer Res. 1993;53(6):1421–30.PubMedGoogle Scholar
  81. 81.
    Filleur S, et al. In vivo mechanisms by which tumors producing thrombospondin 1 bypass its inhibitory effects. Genes Dev. 2001;15(11):1373–82.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Kalas W, Klement P, Rak J. Downregulation of the angiogenesis inhibitor thrombospondin 1 in fibroblasts exposed to platelets and their related phospholipids. Biochem Biophys Res Commun. 2005;334(2):549–54.PubMedCrossRefGoogle Scholar
  83. 83.
    Kalas W, et al. Oncogenes and Angiogenesis: down-regulation of thrombospondin-1 in normal fibroblasts exposed to factors from cancer cells harboring mutant ras. Cancer Res. 2005;65(19):8878–86.PubMedCrossRefGoogle Scholar
  84. 84.
    Elenbaas B, Weinberg RA. Heterotypic signaling between epithelial tumor cells and fibroblasts in carcinoma formation. Exp Cell Res. 2001;264(1):169–84.PubMedCrossRefGoogle Scholar
  85. 85.
    Durning P, Schor SL, Sellwood RA. Fibroblasts from patients with breast cancer show abnormal migratory behaviour in vitro. Lancet. 1984;2(8408):890–2.PubMedCrossRefGoogle Scholar
  86. 86.
    Schor SL, et al. Foetal and cancer patient fibroblasts produce an autocrine migration-stimulating factor not made by normal adult cells. J Cell Sci. 1988;90(Pt 3):391–9.PubMedGoogle Scholar
  87. 87.
    Schor SL, Schor AM, Rushton G. Fibroblasts from cancer patients display a mixture of both foetal and adult-like phenotypic characteristics. J Cell Sci. 1988;90(Pt 3):401–7.PubMedGoogle Scholar
  88. 88.
    Tsukada T, et al. HHF35, a muscle actin-specific monoclonal antibody. II. Reactivity in normal, reactive, and neoplastic human tissues. Am J Pathol. 1987;127(2):389–402.PubMedPubMedCentralGoogle Scholar
  89. 89.
    Normanno N, et al. Expression of messenger RNA for amphiregulin, heregulin, and cripto-1, three new members of the epidermal growth factor family, in human breast carcinomas. Breast Cancer Res Treat. 1995;35(3):293–7.PubMedCrossRefGoogle Scholar
  90. 90.
    Panico L, et al. Differential immunohistochemical detection of transforming growth factor alpha, amphiregulin and CRIPTO in human normal and malignant breast tissues. Int J Cancer. 1996;65(1):51–6.PubMedCrossRefGoogle Scholar
  91. 91.
    Jin L, et al. Expression of scatter factor and c-met receptor in benign and malignant breast tissue. Cancer. 1997;79(4):749–60.PubMedCrossRefGoogle Scholar
  92. 92.
    Montesano R, Schaller G, Orci L. Induction of epithelial tubular morphogenesis in vitro by fibroblast-derived soluble factors. Cell. 1991;66(4):697–711.PubMedCrossRefGoogle Scholar
  93. 93.
    Seslar SP, Nakamura T, Byers SW. Regulation of fibroblast hepatocyte growth factor/scatter factor expression by human breast carcinoma cell lines and peptide growth factors. Cancer Res. 1993;53(6):1233–8.PubMedGoogle Scholar
  94. 94.
    To CT, Tsao MS. The roles of hepatocyte growth factor/scatter factor and met receptor in human cancers (Review). Oncol Rep. 1998;5(5):1013–24.PubMedGoogle Scholar
  95. 95.
    Vande Woude GF, et al. Met-HGF/SF: tumorigenesis, invasion and metastasis. In: Ciba foundation symposium, vol. 212; 1997. p. 119–30. discussion 130–2, 148–54.Google Scholar
  96. 96.
    Cullen KJ, et al. Insulin-like growth factor expression in breast cancer epithelium and stroma. Breast Cancer Res Treat. 1992;22(1):21–9.PubMedCrossRefGoogle Scholar
  97. 97.
    Ellis MJ, et al. Insulin-like growth factor mediated stromal-epithelial interactions in human breast cancer. Breast Cancer Res Treat. 1994;31(2–3):249–61.PubMedCrossRefGoogle Scholar
  98. 98.
    Yee D, et al. Analysis of insulin-like growth factor I gene expression in malignancy: evidence for a paracrine role in human breast cancer. Mol Endocrinol. 1989;3(3):509–17.PubMedCrossRefGoogle Scholar
  99. 99.
    Basset P, et al. A novel metalloproteinase gene specifically expressed in stromal cells of breast carcinomas. Nature. 1990;348(6303):699–704.PubMedCrossRefGoogle Scholar
  100. 100.
    Basset P, et al. Stromelysin-3 in stromal tissue as a control factor in breast cancer behavior. Cancer. 1994;74(3 Suppl):1045–9.PubMedCrossRefGoogle Scholar
  101. 101.
    Chambers AF, Matrisian LM. Changing views of the role of matrix metalloproteinases in metastasis. J Natl Cancer Inst. 1997;89(17):1260–70.PubMedCrossRefGoogle Scholar
  102. 102.
    Engel G, et al. Correlation between stromelysin-3 mRNA level and outcome of human breast cancer. Int J Cancer. 1994;58(6):830–5.PubMedCrossRefGoogle Scholar
  103. 103.
    Heppner KJ, et al. Expression of most matrix metalloproteinase family members in breast cancer represents a tumor-induced host response. Am J Pathol. 1996;149(1):273–82.PubMedPubMedCentralGoogle Scholar
  104. 104.
    Lochter A, et al. The significance of matrix metalloproteinases during early stages of tumor progression. Ann N Y Acad Sci. 1998;857:180–93.PubMedCrossRefGoogle Scholar
  105. 105.
    Masson R, et al. In vivo evidence that the stromelysin-3 metalloproteinase contributes in a paracrine manner to epithelial cell malignancy. J Cell Biol. 1998;140(6):1535–41.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    McCawley LJ, Matrisian LM. Matrix metalloproteinases: multifunctional contributors to tumor progression. Mol Med Today. 2000;6(4):149–56.PubMedCrossRefGoogle Scholar
  107. 107.
    Newell KJ, et al. Expression and localization of matrix-degrading metalloproteinases during colorectal tumorigenesis. Mol Carcinog. 1994;10(4):199–206.PubMedCrossRefGoogle Scholar
  108. 108.
    Wolf C, et al. Stromelysin 3 belongs to a subgroup of proteinases expressed in breast carcinoma fibroblastic cells and possibly implicated in tumor progression. Proc Natl Acad Sci U S A. 1993;90(5):1843–7.PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Sappino AP, et al. Smooth-muscle differentiation in stromal cells of malignant and non-malignant breast tissues. Int J Cancer. 1988;41(5):707–12.PubMedCrossRefGoogle Scholar
  110. 110.
    Ronnov-Jessen L, Petersen OW. Induction of alpha-smooth muscle actin by transforming growth factor-beta 1 in quiescent human breast gland fibroblasts. Implications for myofibroblast generation in breast neoplasia. Lab Investig. 1993;68(6):696–707.PubMedGoogle Scholar
  111. 111.
    Orimo A, Weinberg RA. Stromal fibroblasts in cancer: a novel tumor-promoting cell type. Cell Cycle. 2006;5(15):1597–601.PubMedCrossRefGoogle Scholar
  112. 112.
    Orimo A, et al. Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell. 2005;121(3):335–48.PubMedCrossRefGoogle Scholar
  113. 113.
    Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100(1):57–70.PubMedCrossRefGoogle Scholar
  114. 114.
    Chiquet-Ehrismann R, et al. Tenascin: an extracellular matrix protein involved in tissue interactions during fetal development and oncogenesis. Cell. 1986;47(1):131–9.PubMedCrossRefGoogle Scholar
  115. 115.
    Inaguma Y, et al. Epithelial induction of stromal tenascin in the mouse mammary gland: from embryogenesis to carcinogenesis. Dev Biol. 1988;128(2):245–55.PubMedCrossRefGoogle Scholar
  116. 116.
    Brunner A, et al. Prognostic significance of tenascin-C expression in superficial and invasive bladder cancer. J Clin Pathol. 2004;57(9):927–31.PubMedPubMedCentralCrossRefGoogle Scholar
  117. 117.
    Mackie EJ, et al. Tenascin is a stromal marker for epithelial malignancy in the mammary gland. Proc Natl Acad Sci U S A. 1987;84(13):4621–5.PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Brown EB, et al. Measurement of macromolecular diffusion coefficients in human tumors. Microvasc Res. 2004;67(3):231–6.PubMedCrossRefGoogle Scholar
  119. 119.
    Netti PA, et al. Role of extracellular matrix assembly in interstitial transport in solid tumors. Cancer Res. 2000;60(9):2497–503.PubMedGoogle Scholar
  120. 120.
    Grum-Schwensen B, et al. Suppression of tumor development and metastasis formation in mice lacking the S100A4(mts1) gene. Cancer Res. 2005;65(9):3772–80.PubMedCrossRefGoogle Scholar
  121. 121.
    Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet. 2001;357(9255):539–45.PubMedCrossRefGoogle Scholar
  122. 122.
    Balkwill F, Charles KA, Mantovani A. Smoldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer Cell. 2005;7(3):211–7.PubMedCrossRefGoogle Scholar
  123. 123.
    Mantovani A, et al. The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol. 2004;25(12):677–86.PubMedCrossRefGoogle Scholar
  124. 124.
    Sher A, Pearce E, Kaye P. Shaping the immune response to parasites: role of dendritic cells. Curr Opin Immunol. 2003;15(4):421–9.PubMedCrossRefGoogle Scholar
  125. 125.
    Goerdt S, Orfanos CE. Other functions, other genes: alternative activation of antigen-presenting cells. Immunity. 1999;10(2):137–42.PubMedCrossRefGoogle Scholar
  126. 126.
    Gordon S. Alternative activation of macrophages. Nat Rev Immunol. 2003;3(1):23–35.PubMedCrossRefGoogle Scholar
  127. 127.
    Mantovani A, et al. Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol. 2002;23(11):549–55.PubMedCrossRefGoogle Scholar
  128. 128.
    Mosser DM. The many faces of macrophage activation. J Leukoc Biol. 2003;73(2):209–12.PubMedCrossRefGoogle Scholar
  129. 129.
    Crowther M, et al. Microenvironmental influence on macrophage regulation of angiogenesis in wounds and malignant tumors. J Leukoc Biol. 2001;70(4):478–90.PubMedGoogle Scholar
  130. 130.
    Dong Z, et al. Angiostatin-mediated suppression of cancer metastases by primary neoplasms engineered to produce granulocyte/macrophage colony-stimulating factor. J Exp Med. 1998;188(4):755–63.PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.
    Dong Z, et al. Macrophage-derived metalloelastase is responsible for the generation of angiostatin in Lewis lung carcinoma. Cell. 1997;88(6):801–10.PubMedCrossRefGoogle Scholar
  132. 132.
    O’Reilly MS, et al. Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell. 1994;79(2):315–28.PubMedCrossRefGoogle Scholar
  133. 133.
    Norrby K. Mast cells and angiogenesis. APMIS. 2002;110(5):355–71.PubMedCrossRefGoogle Scholar
  134. 134.
    Kirshenbaum AS, et al. Demonstration that human mast cells arise from a progenitor cell population that is CD34(+), c-kit(+), and expresses aminopeptidase N (CD13). Blood. 1999;94(7):2333–42.PubMedGoogle Scholar
  135. 135.
    Matrisian LM. Metalloproteinases and their inhibitors in matrix remodeling. Trends Genet. 1990;6(4):121–5.PubMedCrossRefGoogle Scholar
  136. 136.
    Tazzyman S, Lewis CE, Murdoch C. Neutrophils: key mediators of tumour angiogenesis. Int J Exp Pathol. 2009;90(3):222–31.PubMedPubMedCentralCrossRefGoogle Scholar
  137. 137.
    Coussens LM, et al. Inflammatory mast cells up-regulate angiogenesis during squamous epithelial carcinogenesis. Genes Dev. 1999;13(11):1382–97.PubMedPubMedCentralCrossRefGoogle Scholar
  138. 138.
    Coussens LM, et al. MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis. Cell. 2000;103(3):481–90.PubMedPubMedCentralCrossRefGoogle Scholar
  139. 139.
    Gruber BL, Marchese MJ, Kew R. Angiogenic factors stimulate mast-cell migration. Blood. 1995;86(7):2488–93.PubMedGoogle Scholar
  140. 140.
    Gruber BL, Marchese MJ, Kew RR. Transforming growth factor-beta 1 mediates mast cell chemotaxis. J Immunol. 1994;152(12):5860–7.PubMedGoogle Scholar
  141. 141.
    Soucek L, et al. Mast cells are required for angiogenesis and macroscopic expansion of Myc-induced pancreatic islet tumors. Nat Med. 2007;13(10):1211–8.PubMedCrossRefGoogle Scholar
  142. 142.
    Pittenger MF, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284(5411):143–7.PubMedCrossRefGoogle Scholar
  143. 143.
    Civin CI, et al. Highly purified CD34-positive cells reconstitute hematopoiesis. J Clin Oncol. 1996;14(8):2224–33.PubMedCrossRefGoogle Scholar
  144. 144.
    Dennis JE, Charbord P. Origin and differentiation of human and murine stroma. Stem Cells. 2002;20(3):205–14.PubMedCrossRefGoogle Scholar
  145. 145.
    Hall B, Andreeff M, Marini F. The participation of mesenchymal stem cells in tumor stroma formation and their application as targeted-gene delivery vehicles. Handb Exp Pharmacol. 2007;180:263–83.CrossRefGoogle Scholar
  146. 146.
    Schichor C, et al. Vascular endothelial growth factor A contributes to glioma-induced migration of human marrow stromal cells (hMSC). Exp Neurol. 2006;199(2):301–10.PubMedCrossRefGoogle Scholar
  147. 147.
    Birnbaum T, et al. Malignant gliomas actively recruit bone marrow stromal cells by secreting angiogenic cytokines. J Neuro-Oncol. 2007;83(3):241–7.CrossRefGoogle Scholar
  148. 148.
    Kidd S, et al. The (in) auspicious role of mesenchymal stromal cells in cancer: be it friend or foe. Cytotherapy. 2008;10(7):657–67.PubMedCrossRefGoogle Scholar
  149. 149.
    Spaeth E, et al. Inflammation and tumor microenvironments: defining the migratory itinerary of mesenchymal stem cells. Gene Ther. 2008;15(10):730–8.PubMedCrossRefGoogle Scholar
  150. 150.
    Dwyer RM, et al. Monocyte chemotactic protein-1 secreted by primary breast tumors stimulates migration of mesenchymal stem cells. Clin Cancer Res. 2007;13(17):5020–7.PubMedCrossRefGoogle Scholar
  151. 151.
    Coffelt SB, et al. The pro-inflammatory peptide LL-37 promotes ovarian tumor progression through recruitment of multipotent mesenchymal stromal cells. Proc Natl Acad Sci U S A. 2009;106(10):3806–11.PubMedPubMedCentralCrossRefGoogle Scholar
  152. 152.
    Sun B, et al. Correlation between melanoma angiogenesis and the mesenchymal stem cells and endothelial progenitor cells derived from bone marrow. Stem Cells Dev. 2005;14(3):292–8.PubMedCrossRefGoogle Scholar
  153. 153.
    Beckermann BM, et al. VEGF expression by mesenchymal stem cells contributes to angiogenesis in pancreatic carcinoma. Br J Cancer. 2008;99(4):622–31.PubMedPubMedCentralCrossRefGoogle Scholar
  154. 154.
    Suratt BT, et al. Role of the CXCR4/SDF-1 chemokine axis in circulating neutrophil homeostasis. Blood. 2004;104(2):565–71.PubMedCrossRefGoogle Scholar
  155. 155.
    Friedman AD. Transcriptional regulation of granulocyte and monocyte development. Oncogene. 2002;21(21):3377–90.PubMedCrossRefGoogle Scholar
  156. 156.
    Kanwar VS, Cairo MS. Neonatal neutrophil maturation, kinetics, and function. In: Abramson JS, Wheeler JG, editors. The Neutrophil. New York: Oxford University Press; 1993. p. 1–16.Google Scholar
  157. 157.
    Steele RW, et al. Functional capacity of marginated and bone marrow reserve granulocytes. Infect Immun. 1987;55(10):2359–63.PubMedPubMedCentralGoogle Scholar
  158. 158.
    Suwa T, et al. Interleukin-6 induces demargination of intravascular neutrophils and shortens their transit in marrow. Am J Physiol Heart Circ Physiol. 2000;279(6):H2954–60.PubMedCrossRefGoogle Scholar
  159. 159.
    Bellocq A, et al. Neutrophil alveolitis in bronchioloalveolar carcinoma: induction by tumor-derived interleukin-8 and relation to clinical outcome. Am J Pathol. 1998;152(1):83–92.PubMedPubMedCentralGoogle Scholar
  160. 160.
    Mentzel T, et al. The association between tumour progression and vascularity in myxofibrosarcoma and myxoid/round cell liposarcoma. Virchows Arch. 2001;438(1):13–22.PubMedCrossRefGoogle Scholar
  161. 161.
    Mhawech-Fauceglia P, et al. The source of APRIL up-regulation in human solid tumor lesions. J Leukoc Biol. 2006;80(4):697–704.PubMedCrossRefGoogle Scholar
  162. 162.
    Nielsen BS, et al. 92 kDa type IV collagenase (MMP-9) is expressed in neutrophils and macrophages but not in malignant epithelial cells in human colon cancer. Int J Cancer. 1996;65(1):57–62.PubMedCrossRefGoogle Scholar
  163. 163.
    Xie K. Interleukin-8 and human cancer biology. Cytokine Growth Factor Rev. 2001;12(4):375–91.PubMedCrossRefGoogle Scholar
  164. 164.
    Coussens LM, Werb Z. Matrix metalloproteinases and the development of cancer. Chem Biol. 1996;3(11):895–904.PubMedCrossRefGoogle Scholar
  165. 165.
    Gaudry M, et al. Intracellular pool of vascular endothelial growth factor in human neutrophils. Blood. 1997;90(10):4153–61.PubMedGoogle Scholar
  166. 166.
    Huang S, et al. Contributions of stromal metalloproteinase-9 to angiogenesis and growth of human ovarian carcinoma in mice. J Natl Cancer Inst. 2002;94(15):1134–42.PubMedCrossRefGoogle Scholar
  167. 167.
    Nozawa H, Chiu C, Hanahan D. Infiltrating neutrophils mediate the initial angiogenic switch in a mouse model of multistage carcinogenesis. Proc Natl Acad Sci U S A. 2006;103(33):12493–8.PubMedPubMedCentralCrossRefGoogle Scholar
  168. 168.
    Clark RA, Klebanoff SJ. Neutrophil-mediated tumor cell cytotoxicity: role of the peroxidase system. J Exp Med. 1975;141(6):1442–7.PubMedCrossRefGoogle Scholar
  169. 169.
    Di Carlo E, et al. The intriguing role of polymorphonuclear neutrophils in antitumor reactions. Blood. 2001;97(2):339–45.PubMedCrossRefGoogle Scholar
  170. 170.
    Ai S, et al. Angiogenic activity of bFGF and VEGF suppressed by proteolytic cleavage by neutrophil elastase. Biochem Biophys Res Commun. 2007;364(2):395–401.PubMedCrossRefGoogle Scholar
  171. 171.
    Scapini P, et al. Generation of biologically active angiostatin kringle 1-3 by activated human neutrophils. J Immunol. 2002;168(11):5798–804.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  1. 1.Department of Surgery Vascular Biology ProgramBoston Children’s Hospital, Harvard Medical SchoolBostonUSA

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