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Targeting the Tumor Microenvironment (Stroma) for Treatment of Metastasis

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Angiogenesis

The major cause of death from cancer is metastases that are resistant to conventional therapies. Metastases can be located in different organs and in different regions of the same organ that influence the response to therapy. Primary tumor in general and metastatic lesions in particular are biologically heterogeneous and contain multiple cell populations with diverse characteristics of growth rate, karyotype, cell surface receptors, antigenicity, immunogenicity, enzymes, hormone receptors, sensitivity to different cytotoxic drugs, production of extracellular matrix proteins, adhesion molecules, angiogenic potential, invasiveness, and metastatic potential. The outcome of metastasis depends on multiple interactions of metastatic cells with homeostatic mechanisms, which tumor cells often usurp. At the primary metastatic sites, tumor cells interact with host cells, such as endothelial cells, pericytes, epithelial cells, fibroblasts, myoepithelial cells, and leukocytes. The tissues composed by these normal cells are biologically unique, and the organ microenvironments they provide for tumor cells are also unique.

The pathogenesis of a metastasis consists of many sequential steps that must be completed to produce clinically relevant lesions. Preferential metastasis of tumor cells to certain organs is independent of vascular anatomy, rate of blood flow, and number of tumor cells delivered to each organ. The outcome of metastasis depends on multiple continuous interactions between unique subpopulations of tumor cells (“seed”) and specific host factors within the organ microenvironment, such as vasculature (“soil”).

Understanding the mechanisms responsible for the development of biological heterogeneity in primary cancers and metastases, and the processes that regulate tumor cell dissemination to and proliferation in distant tissues, is a major goal of research. For many years, all of our efforts to treat cancer metastases have concentrated on the inhibition or destruction of tumor cells. Because all cells in the body depend on an adequate supply of oxygen and nutrients, and on the ability of the circulatory system to remove toxic molecules, therapeutic regimens directed against tumor-associated endothelial cell can destroy tumor cells regardless of their biologic heterogeneity. New strategies to treat tumor cells by modulating their interaction with the organ microenvironment and by targeting receptors expressed on tumor-associated endothelial cells present unprecedented possibilities for the treatment of cancer metastasis.

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References

  1. Fidler IJ. Critical factors in the biology of human cancer metastasis: twenty-eighth GHA Clowes memorial award lecture. Cancer Res 1990; 50:6130–38.

    PubMed  CAS  Google Scholar 

  2. Fidler IJ. The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited (Timeline). Nat. Rev. Cancer 2003; 3:453–8.

    Article  PubMed  CAS  Google Scholar 

  3. Fidler IJ. Biology of cancer metastasis. In: Abeloff MD, Armitage JO, Niederhuber JE, Kastan MB, McKenna WG, editors. Clinical oncology, 3rd edition. Philadelphia, PA: Elsevier Science, 2004:59–79.

    Google Scholar 

  4. Liotta LA, Steeg PS, Stetler-Stevenson WG. Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell 1991; 64:327–36.

    Article  PubMed  CAS  Google Scholar 

  5. Weiss L. Metastasis of cancer: a conceptual history from antiquity to the 1990s. Cancer Metastasis Rev 2000; 19:193–400.

    Article  Google Scholar 

  6. Fidler IJ. Metastasis: quantitative analysis of distribution and fate of tumor emboli labeled with 125I-5-iodo-2’-deoxyuridine. J Natl Cancer Inst 1970; 45:773–82.

    PubMed  CAS  Google Scholar 

  7. Paget S. The distribution of secondary growths in cancer of the breast. Lancet 1889; 1:571–3.

    Article  Google Scholar 

  8. Hart IR, Fidler IJ. Role of organ selectivity in the determination of metastatic patterns of the B16 melanoma. Cancer Res 1980; 40:2281–7.

    PubMed  CAS  Google Scholar 

  9. Tarin D, Price JE, Kettlewell MG, et al. Mechanisms of human tumor metastasis studied in patients with peritoneovenous shunts. Cancer Res 1984; 44:3584–92.

    PubMed  CAS  Google Scholar 

  10. Schackert G, Fidler IJ. Site-specific metastasis of moue melanomas and a fibrosarcoma in the brain or meninges of syngeneic animals. Cancer Res 1988; 48:3478–84.

    PubMed  CAS  Google Scholar 

  11. Schackert G, Price JE, Zhang RD, et al. Regional growth of different human melanoma as metastasis in the brain of nude mice. Am J Pathol 1990; 136:95–102.

    PubMed  CAS  Google Scholar 

  12. Langley RR, Ramirez KM, Tsan RZ, et al. Tissue-specific microvascular endothelial cell lines from H-2k b-tsA58 mice for studies of angiogenesis and metastasis. Cancer Res 2003; 63:2971–6.

    PubMed  CAS  Google Scholar 

  13. Langley RR, Fan D, Tsan RZ, et al. 2004. Activation of the platelet- derived growth factor receptor enhances survival of murine bone endothelial cells. Cancer Res (Adv in Brief) 2004; 64: 3727–30.

    Article  CAS  Google Scholar 

  14. Fidler IJ. The organ microenvironment and cancer metastasis (Review). Differentiation 2002; 70:498–505.

    Article  PubMed  Google Scholar 

  15. Fidler IJ, Yano S, Zhang RD, et al. The seed and soil hypothesis: vascularization and brain metastases (Personal View). Lancet Oncol 2002; 3:53–7.

    Article  PubMed  CAS  Google Scholar 

  16. Folkman J. Angiogenesis in cancer, vascular, rheumatoid, and other diseases. Nat Med 1995; 1:27–31.

    Article  PubMed  CAS  Google Scholar 

  17. Singh RK, Bucana CD, Gutman M, et al. Organ site-dependent expression of basic fibroblast growth factor in human renal cell carcinoma cells. Am J Pathol 1994; 145:365–74.

    PubMed  CAS  Google Scholar 

  18. Singh RK, Gutman M, Bucana CD, et al. Interferons alpha and beta downregulate the expression of basic fibroblast growth factor in human carcinomas. Proc Natl Acad Sci USA 1995; 92: 4562–6.

    Article  PubMed  CAS  Google Scholar 

  19. Singh RK, Gutman M, Radinsky R, et al. Expression of interleukin 8 correlates with the metastatic potential of human melanoma cells in nude mice. Cancer Res 1994; 54:3242–7.

    PubMed  CAS  Google Scholar 

  20. Nilsson MB, Langley RR, Fidler IJ. Interleukin-6, secreted by human ovarian carcinoma cells, is a potent proangiogenic cytokine. Cancer Res 2005; 65:10794–800.

    Article  PubMed  CAS  Google Scholar 

  21. Nanus DM, Schmitz-Drager BJ, Motzer RJ, et al. Expression of basic fibroblast growth factor in primary human renal tumors: correlation with poor survival. J Natl Cancer Inst 1994; 85: 1587–99.

    Google Scholar 

  22. Nguyen M, Watanabe H, Budson AE, et al. Elevated levels of an angiogenic peptide, basic fibroblast growth factor, in the urine of patients with a wide spectrum of cancers. J Natl Cancer Inst 1994; 86:356–61.

    Article  PubMed  CAS  Google Scholar 

  23. Leek RD, Harris AL, Lewis CE. Cytokine networks in solid human tumors: regulation of angiogenesis. J Leukoc Biol 1994; 56:423–35.

    PubMed  CAS  Google Scholar 

  24. Gutman M, Singh RK, Bucana CD, et al. Regulation of IL-8 expression in human melanoma cells by the organ environment. Cancer Res 1995; 55:2470–5.

    PubMed  CAS  Google Scholar 

  25. Hirano T, Yasukawa K, Harada H, et al. Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin. Nature 1986; 324:73–6.

    Article  PubMed  CAS  Google Scholar 

  26. Hirano T. Interleukin 6 and its receptor: ten years later. Int Rev Immunol 1998;16:249–84.

    Article  PubMed  CAS  Google Scholar 

  27. Salgado R, Junius S, Benoy I, et al. Circulating interleukin-6 predicts survival in patients with metastatic breast cancer. Int J Cancer 2003; 103:642–6.

    Article  PubMed  CAS  Google Scholar 

  28. Culig Z, Bartsch G, Hobisch A. Interleukin-6 regulates androgen receptor activity and prostate cancer cell growth. Mol Cell Endocrinol 2002; 197:231–8.

    Article  PubMed  CAS  Google Scholar 

  29. Plante M, Rubin SC, Wong GY, et al. Interleukin-6 level in serum and ascites as a prognostic factor in patients with epithelial ovarian cancer. Cancer 1994; 73:1882–8.

    Article  PubMed  CAS  Google Scholar 

  30. Tempfer C, Zeisler H, Sliutz G, et al. Serum evaluation of interleukin 6 in ovarian cancer patients. Gynecol Oncol 1997; 66: 27–30.

    Article  PubMed  CAS  Google Scholar 

  31. Moretti S, Chiarugi A, Semplici F, et al. Serum imbalance of cytokines in melanoma patients. Melanoma Res 2001; 11: 395–9.

    Article  PubMed  CAS  Google Scholar 

  32. Jee SH, Shen SC, Chiu HC, et al. Overexpression of interleukin-6 in human basal cell carcinoma cell lines increases anti-apoptotic activity and tumorigenic potency. Oncogene 2001; 20:198–208.

    Article  PubMed  CAS  Google Scholar 

  33. Su J, Kai K, Chen C, et al. A novel peptide specifically binding to interleukin-6 receptor (gp80) inhibits angiogenesis and tumor growth. Cancer Res 2005; 65:4827–35.

    Article  PubMed  CAS  Google Scholar 

  34. Fidler IJ, Langley RR, Kerbel RS, et al. Biology of cancer: angiogenesis. In: DeVita VT Jr, Hellman S, Rosenberg SA, editors. Cancer: principles and practice of oncology, 7th edition. Philadelphia, PA: Lippincott & Wilkins, 2005: 129–137.

    Google Scholar 

  35. Jemal A, Tiwari RC, Murray T, et al. Cancer statistics, 2004. CA Cancer J Clin 2004; 54:8–29.

    Article  PubMed  Google Scholar 

  36. Li D, Xie K, Wolff R, et al. Pancreatic cancer. Lancet 2004; 363:1049–57.

    Article  PubMed  CAS  Google Scholar 

  37. Burris HA III, Moore MJ, Andersen J, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 1997; 15:2403–13.

    PubMed  CAS  Google Scholar 

  38. Abbruzzese JL. New application of gemcitabine and future directions in the management of pancreatic cancer. Cancer 2002; 95:941–5.

    Article  PubMed  CAS  Google Scholar 

  39. Perugini RA, McDade TP, Vittimberga FJ, et al. Pancreatic cancer cell proliferation is phosphatidylinositol 3-kinase dependent. J Surg Res 2000; 90:29–44.

    Article  CAS  Google Scholar 

  40. Nicholson KM, Anderson NG. The protein kinase B/Akt signaling pathway in human malignancy. Cell Signal 2002; 14: 381–95.

    Article  PubMed  CAS  Google Scholar 

  41. Wang W, Abbruzzese JL, Evans DB, et al. The nuclear factor-kappa B RelA transcription factor is constitutively activated in human pancreatic adenocarcinoma cells. Clin Cancer Res 1999; 5:119–27.

    PubMed  CAS  Google Scholar 

  42. Douziech N, Calvo E, Laine J, et al. Activation of MAP kinases in growth responsive pancreatic cancer cells. Cell Signal 1999; 11:591–602.

    Article  PubMed  CAS  Google Scholar 

  43. Ghaneh P, Kawesha A, Evans JD, et al. Molecular prognostic markers in pancreatic cancer. J Hepatobiliary Pancreat Surg 2002; 9:1–11.

    Article  PubMed  Google Scholar 

  44. Kuwahara K, Sasaki T, Kuwada Y, et al. Expressions of angiogenic factors in pancreatic ductal carcinoma: a correlative study with clinico-pathologic parameters and patient survival. Pancreas 2003; 26:344–9.

    Article  PubMed  CAS  Google Scholar 

  45. Yamanaka Y, Friess H, Kobrin MS, et al. Coexpression of epidermal growth factor receptor and ligands in human pancreatic cancer is associated with enhanced tumor aggressiveness. Anticancer Res 1993; 13:565–9.

    PubMed  CAS  Google Scholar 

  46. Ferrara N, Alitalo K. Clinical applications of angiogenic growth factors and their inhibitors. Nat Med 1999; 5:1359–64.

    Article  PubMed  CAS  Google Scholar 

  47. Gerber HP, Dixit V, Ferrara N. Vascular endothelial growth factor induces expression of the antiapoptotic proteins Bcl-2 and A1 in vascular endothelial cells. J Biol Chem 1998; 273:13313–6.

    Article  PubMed  CAS  Google Scholar 

  48. Tran J, Rak J, Sheehan C, et al. Marked induction of the IAP family antiapoptotic proteins survivin and XIAP by VEGF in vascular endothelial cells. Biochem Biophys Res Commun 1999; 264:781–8.

    Article  PubMed  CAS  Google Scholar 

  49. Kim SJ, Uehara H, Yazici S, et al. Modulation of bone microenvironment with Zoledronate enhances the therapeutic effects of STI571 and Paclitaxel against experimental bone metastasis of human prostate cancer. Cancer Res 2005; 65:3707–15.

    Article  PubMed  CAS  Google Scholar 

  50. Ebert M, Yokoyama M, Friess H, et al. Induction of platelet-derived growth factor A and B chains and over-expression of their receptors in human pancreatic cancer. Int J Cancer 1995; 62:529–35.

    Article  PubMed  CAS  Google Scholar 

  51. Hwang RF, Yokoi K, Bucana CD, et al. Inhibition of platelet-derived growth factor receptor phosphorylation by STI571 (Gleevec) reduces growth and metastasis of human pancreatic carcinoma in an orthotopic nude mouse model. Clin Cancer Res 2003; 9:6534–44.

    PubMed  CAS  Google Scholar 

  52. Ostman A. PDGF receptors-mediators of autocrine tumor growth and regulators of tumor vasculature and stroma. Cytokine Growth Factor Rev 2004; 15(4):275–86.

    Article  PubMed  CAS  Google Scholar 

  53. Heldin C-H, Westermark B. Mechanism of action and in vivo role of platelet-derived growth factor. Physiol Rev 1999; 79: 1283–316.

    PubMed  CAS  Google Scholar 

  54. Bergers G, Song S, Meyer-Morse N, et al. Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors. J Clin Invest 2003; 111(9):1287–95.

    PubMed  CAS  Google Scholar 

  55. Pietras K, Rubin K, Sjoblom T, et al. Inhibition of PDGF receptor signaling in tumor stroma enhances antitumor effect of chemotherapy. Cancer Res 2002; 62:5476–84.

    PubMed  CAS  Google Scholar 

  56. Pietras K. Increasing tumor uptake of anticancer drugs with imatinib. Semin Oncol 2004; 31:18–23.

    Article  PubMed  CAS  Google Scholar 

  57. Buchdunger E, Cioffi CL, Law N, et al. Abl protein-tyrosine kinase inhibitor STI571 inhibits in vitro signal transduction mediated by c-Kit and platelet-derived growth factor receptors. J Pharmacol Exp Ther 2000; 295:139–45.

    PubMed  CAS  Google Scholar 

  58. Traxler P, Allegrini PR, Brandt R, et al. AEE788: a dual family epidermal growth factor receptor/ErbB2 and vascular endothelial growth factor receptor tyrosine kinase inhibitor with antitumor and antiangiogenic activity. Cancer Res 2004; 64:4931–41.

    Article  PubMed  CAS  Google Scholar 

  59. Yokoi K, Sasaki T, Bucana CD, et al. Simultaneous inhibition of EGF-R, VEGF-R, and PDGF-R signaling combined with gemcitabine produces therapy of human pancreatic carcinoma and prolongs survival in an orthotopic nude mouse model. Cancer Res 2005; 65:10371–80.

    Article  PubMed  CAS  Google Scholar 

  60. Gerber HP, McMurtrey A, Kowalski J, et al. Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3’-kinase/Akt signal transduction pathway. Requirement for Flk-1/KDR activation. J Biol Chem 1998; 273:30336–43.

    Article  PubMed  CAS  Google Scholar 

  61. Hobson B, Denekamp J. Endothelial proliferation in tumours and normal tissues: continuous labeling studies. Br J Cancer 1984;49:405–13.

    PubMed  CAS  Google Scholar 

  62. Eberhard A, Kahlert S, Goede V, et al. Heterogeneity of angiogenesis and blood vessel maturation in human tumors: implications for antiangiogenic tumor therapies. Cancer Res 2000; 60:1388–93.

    PubMed  CAS  Google Scholar 

  63. Weber KL, Doucet M, Price JE, et al. Blockade of epidermal growth factor-receptor signaling leads to inhibition of renal cell carcinoma growth in the bone of nude mice. Cancer Res 2003; 63: 2940–7.

    PubMed  CAS  Google Scholar 

  64. Kedar D, Baker CH, Killion JJ, et al. Blockade of the epidermal growth factor receptor signaling inhibits angiogenesis leading to the regression of human renal cell carcinoma growing orthotopically in nude mice. Clin Cancer Res 2002; 8:3592–3600.

    PubMed  CAS  Google Scholar 

  65. Traxler P, Buchdunger E, Furet P, et al. Preclinical profile of PKI166-a novel and potent EGF-R tyrosine kinase inhibitor for clinical development. Clin Cancer Res 1999; 5:3750–8.

    Google Scholar 

  66. Baker CH, Kedar D, McCarty MF, et al. Blockade of epidermal growth factor receptor signaling on tumor cells and tumor-associated endothelial cells for therapy of human carcinomas. Am J Pathol 2002; 161:929–38.

    PubMed  CAS  Google Scholar 

  67. Baker CH, Pino MS, Fidler IJ. Phosphorylated epidermal growth factor receptor on tumor-associated endothelial cells in human renal cell carcinoma is a primary target for therapy by tyrosine kinase inhibitors. Neoplasia 2006; 8: 470–6.

    Article  PubMed  CAS  Google Scholar 

  68. Saltz L, Rubin M, Hochster H, et al. Cetuximab (IMC-225) plus irinotecan (CPT-11) is active in CPT-11-refractory colorectal cancer that expresses epidermal growth factor receptors. Proc Am Soc Clin Oncol 2001; 20:3–7.

    Google Scholar 

  69. Moasser MM, Basso A, Averbuch SD, et al. The tyrosine kinase inhibitor ZD1839 (“Iressa”) inhibits HER2-driven signaling and suppresses the growth of HER2-overexpressing tumor cells. Cancer Res 2001; 61:7184–8.

    PubMed  CAS  Google Scholar 

  70. Solorzano CC, Baker CH, Tsan R, et al. Optimization for the blockade of epidermal growth factor receptor signaling for therapy of human pancreatic carcinoma. Clin Cancer Res 2001; 7:2563–72.

    PubMed  CAS  Google Scholar 

  71. Rak J, Filmus J, Kerbel RS. Reciprocal paracrine interactions between tumor cells and endothelial cells: the ‘angiogenesis progression’ hypothesis. Eur J Cancer 1996; 32A:2438–50.

    Article  PubMed  CAS  Google Scholar 

  72. Yoneda J, Kuniyasu H, Crispens MA, et al. Expression of angiogenesis-related genes and progression of human ovarian carcinomas in nude mice. J Natl Cancer Inst 1998; 90:447–54.

    Article  PubMed  CAS  Google Scholar 

  73. Radinsky R, Risin S, Fan D, et al. Level and function of epidermal growth factor receptor predict the metastatic potential of human colon carcinoma cells. Clin Cancer Res 1995; 1:19–31.

    PubMed  CAS  Google Scholar 

  74. Albanell J, Rojo F, Averbuch S, et al. Pharmacodynamic studies of the epidermal growth factor receptor inhibitor ZD1839 in skin from cancer patients: histopathologic and molecular consequences of receptor inhibition. J Clin Oncol 2002; 20:110–24.

    Article  PubMed  CAS  Google Scholar 

  75. Baselga J, Rischin D, Ranson M, et al. Phase I safety, pharmacokinetic, and pharmacodynamic trial of ZD1839, a selective oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with five selected solid tumor types. J Clin Oncol 2002; 20:4292–302.

    Article  PubMed  CAS  Google Scholar 

  76. Sirotnak FM, Zakowski MF, Miller VA, et al. Efficacy of cytotoxic agents against human tumor xenografts is markedly enhanced by coadministration of ZD1839 (Iressa), an inhibitor of EGF-R tyrosine kinase. Clin Cancer Res 2000; 6:4885–92.

    PubMed  CAS  Google Scholar 

  77. Ciardiello F, Caputo R, Bianco R, et al. Antitumor effect and potentiation of cytotoxic drugs activity in human cancer cells by ZD-1839 (Iressa), an epidermal growth factor receptor-selective tyrosine kinase inhibitor. Clin Cancer Res 2000; 6:2053–63.

    PubMed  CAS  Google Scholar 

  78. Hirata A, Uehara H, Izumi K, et al. Direct inhibition of EGF receptor activation in vascular endothelial cells by gefitinib (“Iressa”, ZD 1839). Cancer Sci 2004; 95:614–8.

    Article  PubMed  CAS  Google Scholar 

  79. Naito S, Walker SM, Fidler IJ. In vivo selection of human renal cell carcinoma cells with high metastatic potential in nude mice. Clin Exp Metastasis 1989; 7:381–9.

    Article  PubMed  CAS  Google Scholar 

  80. Landis SH, Murray T, Bolden-Wingo PA. Cancer statistics, 1999. Cancer 1999; 49:8–31.

    CAS  Google Scholar 

  81. Soh S, Kattan MW, Berkman S, et al. Has there been a recent shift in the pathological features and prognosis of patients treated with radical prostatectomy? J Urol 1997; 157:2212–8.

    Article  PubMed  CAS  Google Scholar 

  82. Barrettoni BA, Carter JR. Mechanisms of cancer metastasis to bone. J Bone Joint Surg Am 1986; 68A:308–12.

    Google Scholar 

  83. Jacobs SC. Spread of prostatic cancer to bone. Urology 1983; 21:337–44.

    Article  PubMed  CAS  Google Scholar 

  84. Huggins C, Hodges CV. Studies on prostate cancer: The effects of castration on advanced carcinoma of the prostate (abstr). Arch Surg 1941; 43:209.

    CAS  Google Scholar 

  85. Byar DP, Corle DK. Hormone therapy for prostate cancer: results of the Veterans Administration Cooperative Urological Research Group studies. NCI Monograph 1988; 7:165–70.

    Google Scholar 

  86. Millikan R, Thall PF, Lee SJ, et al. Randomized multicenter phase II trial of two multicomponent regimens in androgen-independent prostate cancer. J Clin Oncol 2003; 21:878–83.

    Article  PubMed  CAS  Google Scholar 

  87. Smith DC, Esper P, Strawderman M, et al. Phase II trial of oral estramustine, oral etoposide, and intravenous paclitaxel in hormone-refractory prostate cancer. J Clin Oncol 1999; 17: 1664–71.

    PubMed  CAS  Google Scholar 

  88. Kim SJ, Uehara H, Yazici S, et al. Simultaneous blockade of platelet-derived growth factor-receptor and epidermal growth factor-receptor signaling and systemic administration of paclitaxel as therapy for human prostate cancer metastasis in bone of nude mice. Cancer Res 2004; 64:4201–4208.

    Article  PubMed  CAS  Google Scholar 

  89. Yazici S, Kim SJ, Busby JE, et al. Dual inhibition of the epidermal growth factor and vascular endothelial growth factor phosphorylation for antivascular therapy of human prostate cancer in the prostate of nude mice. Prostate 2005; 65:203–15.

    Article  PubMed  CAS  Google Scholar 

  90. Klement G, Baruchel S, Rak J, et al. Continuous low-dose therapy with vinblastine and VEGF receptor-2 antibody induces sustained tumor regression without overt toxicity. J Clin Invest 2000; 105:R15–R24.

    Article  PubMed  CAS  Google Scholar 

  91. Druker BJ, Tamura S, Buchdunger E, et al. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl-positive cells. Nat Med 1996; 2:561–5.

    Article  PubMed  CAS  Google Scholar 

  92. Uehara H, Kim SJ, Karashima T, et al. Effects of blocking platelet-derived growth factor-receptor signaling in a mouse model of prostate cancer bone metastasis. J Natl Cancer Inst 2003; 95:458–70.

    PubMed  CAS  Google Scholar 

  93. Kim SJ, Uehara H, Karashima T, et al. Blockade of epidermal growth factor receptor signaling in tumor cells and tumor-associated endothelial cells for therapy of androgen-independent human prostate cancer growing in the bone of nude mice. Clin Cancer Res 2003; 9:1200–10.

    PubMed  CAS  Google Scholar 

  94. Bruns CJ, Solorzano CC, Harbison MT, et al. Blockade of the epidermal growth factor receptor signaling by a novel tyrosine kinase inhibitor leads to apoptosis of endothelial cells and therapy of human pancreatic carcinoma. Cancer Res 2000;60:2926–35.

    PubMed  CAS  Google Scholar 

  95. Hou X, Johnson AC, Rosner MR. Induction of epidermal growth factor receptor gene transcription by transforming growth factor beta 1: association with loss of protein binding to a negative regulatory element. Cell Growth Differ 1994; 5:801–9.

    PubMed  CAS  Google Scholar 

  96. Saha D, Datta PK, Sheng H, et al. Synergistic induction of cyclo-oxygenase-2 by transforming growth factor-β1 and epidermal growth factor inhibits apoptosis in epithelial cells. Neoplasia 1999; 1:508–17.

    Article  PubMed  CAS  Google Scholar 

  97. Vinals F, Pouyssegur J. Transforming growth factor (TGF)-91 promotes endothelial cell survival during in vitro angiogenesis via an autocrine mechanism implicating TGF-α signaling. Mol Cell Biol 2001; 21:7218–30.

    Article  PubMed  CAS  Google Scholar 

  98. Soory M, Virdi H. Implications of minocycline, platelet-derived growth factor, and transforming growth factor-β on inflammatory repair potential in the periodontium. J Periodontol 1999; 70:1136–43.

    Article  PubMed  CAS  Google Scholar 

  99. Seifert RA, Coats SA, Raines EW, et al. Platelet-derived growth factor (PDGF)-receptor α-subunit mutant and reconstituted cell lines demonstrate that transforming growth factor-β can be mitogenic through PDGF A-chain-dependent and -independent pathways. J Biol Chem 1994; 269:13951–5.

    PubMed  CAS  Google Scholar 

  100. Lorenzo GD, Tortora G, D’Armiento FP, et al. Expression of epidermal growth factor receptor correlates with disease relapse and progression to androgen-independence in human prostate cancer. Clin. Cancer Res 2002; 8:3438–44.

    PubMed  Google Scholar 

  101. Fudge K, Bostwick DG, Stearns ME. Platelet-derived growth factor A and B chains and α and β receptors in prostatic intraepithelial neoplasia. Prostate 1996; 29:282–6.

    Article  PubMed  CAS  Google Scholar 

  102. Levitzki A. Tyrosine kinases as targets for cancer therapy. Eur J Cancer 2002; 38(suppl 5): S11–8.

    Article  PubMed  Google Scholar 

  103. Capdeville R, Buchdunger E, Zimmermann J, et al. Glivec (STI571, imatinib), a rationally developed, targeted anticancer drug. Nat Rev Drug Discov 2002; 1:493–502.

    Article  PubMed  CAS  Google Scholar 

  104. Manley PW, Cowan-Jacob SW, Buchdunger E, et al. Imatinib: a selective tyrosine kinase inhibitor. Eur J Cancer 2002; 38(suppl 5):S19–27.

    Article  PubMed  Google Scholar 

  105. Ulrich A, Coussens L, Hayflick JS, et al. Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells. Nature (Lond) 1984; 309:418–25.

    Article  Google Scholar 

  106. Ciardiello F, Damiano V, Bianco R, et al. Antitumor activity of combined blockade of epidermal growth factor receptor and protein kinase A. J Natl Cancer Inst 1996; 88:1770–6.

    Article  PubMed  CAS  Google Scholar 

  107. Uckun FM, Narla RK, Zeren T, et al. In vivo toxicity, pharmacokinetics, and anticancer activity of Genistein linked to recombinant human epidermal growth factor. Clin Cancer Res 1988; 4:1125–34.

    Google Scholar 

  108. Uckun FM, Narla RK, Jun X, et al. Cytotoxic activity of epidermal growth factor-genistein against breast cancer cells. Clin. Cancer Res 1988; 4:901–12.

    Google Scholar 

  109. Thyberg J. The microtubular cytoskeleton and the initiation of DNA synthesis. Exp Cell Res 1984; 155:1–8.

    Article  PubMed  CAS  Google Scholar 

  110. Yoon SY, Tefferi A, Li CY. Cellular distribution of platelet-derived growth factor, transforming growth factor-β, basic fibroblast growth factor, and their receptors in normal bone marrow. Acta Haematol 2000; 104:151–7.

    Article  PubMed  CAS  Google Scholar 

  111. Saharinen P, Alitalio K. Double target for tumor mass destruction. J Clin Invest 2003; 111:1277–80.

    PubMed  CAS  Google Scholar 

  112. Mathew P, Fidler IJ, Logothetis CJ. Combination Docetaxel and platelet derived growth factor receptor inhibition with imatinib mesylate in prostate cancer. Semin. Oncol 2004; 31:24–9.

    Article  PubMed  CAS  Google Scholar 

  113. Gottesman MM, Pastan I. Biochemistry of multidrug resistance mediated by the multidrug transporter. Annu Rev Biochem 1993; 62:385–427.

    Article  PubMed  CAS  Google Scholar 

  114. Van Brussel JP, Jan Van Steenbrugge G, Van Krimpen C, et al. Expression of multidrug resistance related proteins and proliferative activity is increased in advanced clinical prostate cancer. J Urol 2001; 165:130–5.

    Article  PubMed  CAS  Google Scholar 

  115. Kerbel RS, Folkman J. Clinical translation of angiogenesis inhibitors. Nat Rev Cancer 2002; 2:727–39.

    Article  PubMed  CAS  Google Scholar 

  116. Preise D, Mazor O, Koudinova N, et al. Bypass of tumor drug resistance by antivascular therapy. Neoplasia 2003; 5:475–80.

    PubMed  CAS  Google Scholar 

  117. Kim SJ, Uehara H, Yazici S, et al. Targeting platelet-derived growth factor receptor on endothelial cells of multidrug resistant prostate cancer. J Natl Cancer Inst 2006; 98:783–93.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Cancer Biology, The University of Texas, Houston, TX, USA

    Isaiah J. Fidler, Cheryl Hunt Baker, Kenji Yokoi, Toshio Kuwai, Toru Nakamura, Monique Nilsson, J. Erik Busby, Robert R. Langley & Sun-Jin Kim

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  1. Isaiah J. Fidler
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Editors and Affiliations

  1. Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA

    William D. Figg

  2. Department of Surgery Harvard Medical School and Vascular Biology Program, Children's Hospital Boston, Boston, MA, USA

    Judah Folkman

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© 2008 Springer Science+Business Media, LLC

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Fidler, I.J. et al. (2008). Targeting the Tumor Microenvironment (Stroma) for Treatment of Metastasis. In: Figg, W.D., Folkman, J. (eds) Angiogenesis. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-71518-6_23

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  • DOI: https://doi.org/10.1007/978-0-387-71518-6_23

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-0-387-71517-9

  • Online ISBN: 978-0-387-71518-6

  • eBook Packages: MedicineMedicine (R0)

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