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Growth factors and their receptors as determinants in the proliferation and metastasis of human prostate cancer

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Summary

Prostate adenocarcinoma, the most common tumor occuring among North American men, preferentially metastasizes to bone, where it characteristically forms osteoblastic lesions. The following growth regulatory factors are expressed in some human prostate cancers and/or established cell lines: epidermal growth factor (EGF), transforming growth factor alpha, transforming growth factor beta, basic fibroblast growth factor (bFGF), and insulin-like growth factor. Some of these, especially EGF, bFGF, and TGF-beta, are also implicated in growth regulation in normal and benign hyperplastic prostates. Although evidence fromin vitro study of the small number of prostate cell lines available demonstrates that these growth regulatory pathways are exploited by some of these cells, directin vivo evidence is limited. The development of human prostate cancer cell lines which grow and metastasize in immune-deficient rodents is an advance which now permits experimental analysis of the role of these growth factors in prostatic metastasis, particularly to bone. The progression and metastasis of human prostate cancer results from the complex interactions ofmultiple growth factors, androgens, and cellular communication, which form a dynamic network. Continued progress in the study and treatment of this disease will require new conceptual frameworks as well as successful application of the techniques of molecular and cellular biology.

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References

  1. Boring CC, Squires TS, Tong T: Cancer Statistics 1993. CA 43: 7–26, 1993

    Google Scholar 

  2. Cunha GR, Donjacour AA, Cooke PS, Bigsby RM, Higgins SJ, Sugimura Y: The endocrinology and developmental biology of the prostate. Endocrine Reviews 8: 338–362, 1987

    Google Scholar 

  3. Whitmore W: Natural history and staging of prostatic cancer. Urol Clin N.A. 11: 205–220, 1984

    Google Scholar 

  4. Mundy GR: Mechanisms of osteolytic bone destruction. Bone 12 (Suppl. 1): 51–56, 1991

    Google Scholar 

  5. Jacobs SC: Spread of prostatic cancer to bone. Urology 21: 337–344, 1983

    Google Scholar 

  6. Chung LWK: Fibroblasts are critical determinants in prostatic cancer growth and dissemination. Cancer Met Rev 10: 263–274, 1991

    Google Scholar 

  7. Isaacs JT, Isaacs WB, Schalken J: Comparative aspects of multistep prostatic carcinogenesis in humans and rodents. Prog Clin Biol Res 376: 261–288, 1992

    Google Scholar 

  8. Elson SD, Browne CA, Thorburn GG: Identification of epidermal growth factor-like activity in human male reproductive tissues and fluids. J Clin Endocrinol Metab 48: 673–679, 1984

    Google Scholar 

  9. Peehl DM, Stamey TA: Growth responses of normal, benign hyperplastic, and malignant human prostatic epithelial cellsin vitro to cholera toxin, pituitary extract and hydrocortisone. Prostate 8: 51–61, 1986

    Google Scholar 

  10. Fowler JE, Tau LK, Ghosh L: Epidermal growth factor and prostatic carcinoma: An immunohistochemical study. J Urol 139: 857–861, 1988

    Google Scholar 

  11. Connolly JM, Rose DP: Secretion of epidermal growth factor and related polypeptides by the DU145 human prostate cancer cell line. Prostate 15: 177–186, 1989

    Google Scholar 

  12. Maygarden SJ, Strom SC, Ware JL: Localization of epidermal growth factor receptor by immunohistochemical methods in human prostatic carcinoma, prostatic intraepithelial neoplasia, and benign hyperplasia. Arch Pathol Lab Med 116: 269–273, 1992

    Google Scholar 

  13. Maddy SQ, Chisholm GD, Hawkins RA, Habib FK: Localization of epidermal growth factor receptors in the human prostate by biochemical and immunocytochemical methods. J Endocrinol 1987; 113: 147–153

    Google Scholar 

  14. McNeal JE, Bostwick DG: Intraductal dysplasia: a premalignant lesion of the prostate. Hum Pathol 17: 64–71, 1986

    Google Scholar 

  15. Visakorpi T, Kallionieni OP, Koivula T, Koivula J, Harvey J, Isola J: Expression of epidermal growth factor receptor and ERBB2 (HER-2/NEU) Oncoprotein in prostatic carcinomas. Mod Pathol 5: 643–648, 1992

    Google Scholar 

  16. Ibrahim GK, Kerns BJ, MacDonald JA, Ibrahim SN, Kinney RB, Humphry PA, Robertson CN: Differential immunoreactivity of epidermal growth factor receptor in benign, dysplactic and malignant prostatic tissues. J Urol 149: 170–173, 1993

    Google Scholar 

  17. Eaton CL, Davies P, Phillips MEA: Growth factor involvement and oncogene expression in prostatic tumors. J Steroid Biochem 30: 341–345, 1988

    Google Scholar 

  18. Maddy SQ, Chisholm GD, Busuttil A, Habib FK: Epidermal growth factor receptors in human prostate cancer: correlation with histological differentiation of the tumor. Br J Cancer 60: 41–44, 1989

    Google Scholar 

  19. Morris GL, Dodd JG: Epidermal growth factor receptor mRNA levels in human prostatic tumors and cell lines. J Urol 143: 1272–1274, 1990

    Google Scholar 

  20. Davies P, Eaton CL: Binding of epidermal growth factor by human normal, hypertrophic and carcinomatous prostate. Prostate 14: 123–132, 1989

    Google Scholar 

  21. Schuurmans ALG, Bolt J, Voorhorst M, Blankenstein RA, Mulder E: Regulation of growth and epidermal growth factor receptor levels in LNCaP prostate tumor cells by different steroids. Int J Cancer 42: 917–922, 1988

    Google Scholar 

  22. Derynck R, Goeddel DV, Ullrich A, Gutterman JU, Williams RD, Bringman TS, Beryer WH: Synthesis of messenger RNAs for transforming growth factors alpha and beta and the epidermal growth factor receptor by human tumors. Cancer Res 47: 707–712, 1987

    Google Scholar 

  23. Wilding G, Valerius E, Knabbe C, Gelmann EP: Role of transforming growth factor alpha in human prostate cancer cell growth. The Prostate 15: 1–12, 1989

    Google Scholar 

  24. Hofer D, Sherwood E, Bromberg W, Mendelsohn J, Lee C, Kozlowski J: Autonomous growth of androgen-independent prostatic carcinoma cells: role of transforming growth factor α. Cancer Res 51: 2780–2785, 1991

    Google Scholar 

  25. Derynck R: The physiology of transforming growth factoralpha. Adv Cancer Res 1992; 58: 27–52, 1992

    Google Scholar 

  26. Horoszewicz JS, Leong SS, Kawinski E, Kau JP, Rosenthal H, Chu TM, Mirand EA, Murphy GP: LNCaP model of human prostate carcinoma. Cancer Res 43: 1809–1818, 1983

    Google Scholar 

  27. Connolly JM, Rose DP: Production of transforming growth factor alpha by the androgen responsive LNCaP human prostate cancer cell line. Prostate 16: 209–218, 1990

    Google Scholar 

  28. Kaighn ME, Narayan KS, Ohnuki Y, Lechner JF, Jones LW: Establishment and characterization of a human prostatic carcinoma cell line (PC-3). Invest Urol 17: 16–23, 1979

    Google Scholar 

  29. Stone KR, Mickey DD, Wunderli H, Mickey GM, Paulson DF: Isolation of a human prostatic carcinoma cell line (DU145). Int J Cancer 21: 274–281, 1978

    Google Scholar 

  30. Fong CJ, Sherwood ER, Mendelsohn J, Lee C, Kozlowski JM: Epidermal growth factor receptor monoclonal antibody inhibits constitutive receptor phosphorylation, reduces autonomous growth, and sensitizes androgen-independent prostatic carcinoma cells to tumor necrosis factor α. Cancer Res 52: 5886–5892, 1992

    Google Scholar 

  31. Yamamoto T, Ikawa S, Akiyama T, Sembak, Norman N, Miyajima N, Toyoshima ST: Similarity of protein encoded by the human c-erbB-2 gene to epidermal growth factors. Nature 319: 230–234, 1986

    Google Scholar 

  32. Ware JL, Maygarden SJ, Koontz WW, Jr, Strom SC: Immunohistochemical detection of c-erbB-2 protein in human benign and neoplastic prostate. Human Pathol 22: 254–258, 1991

    Google Scholar 

  33. Zhau XYE, Wan DS, Zhau J, Miller GJ, von Eschenbach AC: Expression of c-erbB-2/neu protooncogene in human prostatic cancer tissues and cell lines. Mol Carcinog 5: 320–327, 1992

    Google Scholar 

  34. Mellon K, Thompson S, Charlton RG, Marsh G, Robinson M, Lane DP, Harris AL, Horne CH, Neal DE: p53, c-erbB-2 and the epidermal growth factor receptor in the benign and malignant prostate. J Urol 147: 496–499, 1992

    Google Scholar 

  35. Kuhn J, Kurnot RA, Sesterhenn IA, et al.: Expression of the c-erbB-2 (HER-2/neu) oncoprotein in human prostatic carcinoma. J Urol, in press

  36. Klotz LH, Auger M, Andrulis I, Srigley J: Molecular analysis of neu, sis, c-myc, fos, and p53 oncogenes in benign prostatic hypertrophy and prostatic carcinoma. J Urol 1990; 143; 401A (Abstract)

    Google Scholar 

  37. Sikes RA, Chung LWK: Acquisition of a tumorigenic phenotype by a rat ventral prostate epithelial cell line expressing a transfected activated neu oncogene. Cancer Res 52: 3174–3181, 1992

    Google Scholar 

  38. Holmes WE, Sliwkowski MX, Akita RW, Henzel WJ, Lee J, Park JW, Yansua D, A. Badi, N. Raab H, Lewis GD: Identification of heregulin, a specific activator of p185-erbB-2. Science 256: 1205–1210, 1992

    Google Scholar 

  39. Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, Levin WJ, Stuent SG, Vdore J, Ullrich A: Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 244: 707–712, 1989

    Google Scholar 

  40. Sporn MB, Roberts A, Wakefield LM, de Crombrugghe B: Some recent advances in the chemistry and biology of transforming growth factor beta. J Cell Biol 105: 1039–1045, 1987

    Google Scholar 

  41. Mori H, Maki M, Oishi K, Jaye M, Igarashi K, Yoshida P, Hatanaka M: Increased expression of genes for basic fibroblast growth factor and transforming growth factor type B2 in human benign prostatic hyperplasia. Prostate 16: 71–80, 1990

    Google Scholar 

  42. Truong LD, Kadmon D, McCune BK, Flanders KL, Scardino PT, Thompson TC: Association of transforming growth factor B1 with prostate cancer: An immunohistochemical study. Human Pathol 24: 4–9, 1993

    Google Scholar 

  43. Wilding G, Zugmeier G, Knabbe C,et al.: Differential effects of transforming growth factor beta on human prostate cancer cellsin vitro. Mol Cell Endoc 62: 79–87, 1989

    Google Scholar 

  44. Schurrmans ALG, Bolt J, Mulder E: Androgens and transforming growth factor B modulate the growth response to epidermal growth factor in human prostatic tumor cells (LNCaP). Mol Cell Endoc 60: 101–104, 1988

    Google Scholar 

  45. Plymate SR, Loop SM, Hoop RC, Wiren KM, Ostenson R, Hryb DJ, Rosner W: Effects of sex hormone binding globulin (SHBG) on human prostatic carcinoma. J Steroid Biochem Mol Biol 40: 833–9, 1991

    Google Scholar 

  46. Watts RG, Ware JL, Levy L, Loop SL, Plymate SR: Transforming growth factor B1 regulation of human prostate cancer. Proc Endocrine Soc p 313, 1992 (Abstract)

  47. Bang Y, Kim SJ, Danielpour D, O'Reilly MA, Kim KY, Myers CE, Trepel JB: Cyclic AMP induces transforming growth factor B2 gene expression and growth arrest in the human androgen-independent prostate carcinoma cell line. Proc Natl Acad Sci 89: 3556–3560, 1992

    Google Scholar 

  48. Kryprianou N, Isaacs JT: Identification of a cellular receptor for transforming growth factor β in rat ventral prostate and its negative regulation by androgens. Endocrinol 123: 2124–2131, 1988

    Google Scholar 

  49. Hoehn W, Schroder FH, Riemann JF, Joebis AC, Hermanek P: Human prostatic adenocarcinoma: some characteristics of a serially transplantable line in nude mice (PC82). Prostate 1: 95–104, 1980

    Google Scholar 

  50. Kryprianou N, English HF, Isaacs JT: Programmed cell death during regression of PC-82 human prostate cancer following androgen ablation. Cancer Res 50: 3748–3753, 1990

    Google Scholar 

  51. Watts RG, Ware JL: Isolation and characterization of transforming growth factor beta response variants from human prostatic tumor cell lines. Prostate 21: 223–237, 1992

    Google Scholar 

  52. Steiner MS, Barrack ER: Transforming growth factor-β1 overproduction in prostate cancer: Effects on growthin vivo andin vitro. Mol Endoc 6: 15–25, 1992

    Google Scholar 

  53. Jacobs SC, Lawson RK: Mitogenic factor in human prostate extracts. Urology 16: 488–491, 1980

    Google Scholar 

  54. Mydlo JH, Michaeli J, Heston WDW, Fair WR: Expression of basic fibroblast growth factor mRNA in benign prostatic hyperplastic and prostatic carcinoma. Prostate 13: 241–247, 1987

    Google Scholar 

  55. Story MT, Sasse J, Jacobs SC, Lawson RK: Prostatic growth factor; purification and structural relationship to brain fibroblast growth factor. Biochemistry 26: 3843–3849, 1987

    Google Scholar 

  56. McKeehan WL, Adams PS: Heparin-binding growth factorprostatropin attenuates inhibition of rat prostate tumors epithelial cell growth by transforming growth factor type beta.In Vitro Cell Dev Biol 24: 243–246, 1988

    Google Scholar 

  57. Perkel VS, Mohan S, Herning SJ, Baylins DJ, Linkhart TA: Human prostatic cancer cells, PC-3, elaborate mitogenic activity which selectively stimulates human bone cells. Cancer Res 50: 6902–6907, 1990

    Google Scholar 

  58. Peehl DM, Wong ST, Bazinet M, Stamey TA:In vitro studies of human prostatic epithelial cells: Attempts to identify distinguishing features of malignant cells. Growth Factors 1: 237–250, 1989

    Google Scholar 

  59. Gleave M, Hsiech JT, Gao C, von Eschenbach AC, Chung LWK: Acceleration of human prostate cancer growthin vivo by factors produced by prostate and bone fibroblasts. Cancer Res 51: 3753–3761, 1991

    Google Scholar 

  60. Muller WJ, Lee FS, Dickson C, Peters G, Pattengale P, Leder P: The int-2 gene product acts as an epithelial growth factor in transgenic mice. EMBO J 9: 907–913, 1990

    Google Scholar 

  61. Yoshida T, Miyagawa K, Odagiri H, Sakamoto H, Little PFR, Terada M., Sugimura T: Genomic sequence of hst, a transforming gene encoding a protein homologous to fibroblast growth factors and the int-2 encoded protein. Proc Natl Acad Sci 84: 7305–7309, 1987

    Google Scholar 

  62. Djakiew D, Delsite R, Pflug B: Regulation of growth by a nerve growth factor-like protein which modulates paracrine interactions between a neoplastic epithelial cell line and stromal cells of the human prostate. Cancer Res 51: 3304–3310, 1991

    Google Scholar 

  63. Grahm LW, Lymph JH, Djakiew P: Distribution of nerve growth factor-like protein and nerve growth factor receptor in human benign prostatic hyperplasia and prostatic adenocarcinoma. J Urol 147: 1444–1447, 1992

    Google Scholar 

  64. Macgrogan D, Saint-André JP, Dicou E: Expression of nerve growth factor and nerve growth factor receptor genes in human tissues and in prostatic adenocarcinoma cell lines. J Neuro Chem 59: 1381–1391, 1992

    Google Scholar 

  65. Cohen P, Peehl DM, Lamson G, Rosenfield RF: Insulin-like growth factors (IGF), IGF receptors, and IGF-binding proteins in primary cultures of prostate epithelial cells. J Clin Endoc Metab 73: 401–407, 1991

    Google Scholar 

  66. Fiorelli G, Debellis A, Longo A, Giannioni S, Natalie A, Constantini A, Vannelli GB, Serio M: Insulin-like growth factor-1 receptors in human hyperplastic prostate tissue: Characterization, tissue localization, and their modulation by chronic treatment with a gonadotrophin releasing analog. Analog J Clin Endocrinol Metab 72: 740–746, 1991

    Google Scholar 

  67. Pietrzkowski Z, Mulholland G, Gomella L, Hameson BA, Weinike D, Baserga R: Inhibition of growth of prostatic cancer cell lines by peptide analogues of insulin-like growth factor I. Cancer Res 53: 1102–1106, 1993

    Google Scholar 

  68. Whitmore W: Natural history and staging of prostatic cancer. Urol Clin North Am 11: 205–220, 1984

    Google Scholar 

  69. Ito YZ, Mashimo S, Nakazato Y: Hormone dependency of a serially transplantable human prostatic cancer (HONDA) in nude mice. Cancer Res 45: 5058–5063, 1985

    Google Scholar 

  70. Itzumi T, Yazaki T, Kanoh S: Establishment of a new prostatic carcinoma cell line (TSU-PR-1). J Urol 137: 1304–1306, 1987

    Google Scholar 

  71. Ware JL, Paulson DF, Mickey GM, Webb KS: Spontaneous metastasis of cells of the human prostate carcinoma cell line PC-3 in athymic nude mice. J Urol 128: 1064–1067, 1982

    Google Scholar 

  72. Kozlowski JM, Fidler IJ, Campbell P: Metastatic behavior of human tumor cell lines grown in the nude mouse. Cancer Res 44: 3522–3529, 1984

    Google Scholar 

  73. Shevrin DH, Kukreja SC, Ghosh L, Lad TE: Development of skeletal metastases by human prostate cancer cells in athymic nude mice. Clin Expl Metastasis 6: 401–409, 1988

    Google Scholar 

  74. Wang M, Stearns ME: Isolation and characterization of PC-3 human prostatic tumor sublines which preferentially metastasize to select organs in S.C.I.D. mice. Differentiation 48: 115–125, 1991

    Google Scholar 

  75. Ware JL, Lieberman AP, Webb KS, Vollmer RT: Factors influencing phenotypic diversity of human prostate carcinoma cells metastasizing in athymic nude mice. Exp Cell Biol 53: 163–169, 1985

    Google Scholar 

  76. Ware JL, Delong ER: Influence of tumor size on human prostate tumor metastasis in athymic nude mice. Br J Cancer 51: 419–423, 1985

    Google Scholar 

  77. Ware JL, Lieberman AP, Webb KS: Metastatic phenotype of human prostate cells in athymic nude mice: alteration by exposure to ethylmethanesulfonate and reversion by 5-azacytidine. Cancer Immunol Immunother 21: 58–62, 1986

    Google Scholar 

  78. Shevrin DH, Gorny KI, Kukreja SC: Patterns of metastasis by the human prostate cancer cell line PC-3 in athymic nude mice. Prostate 15: 187–194, 1989

    Google Scholar 

  79. Stearns ME, Wang M: Regulation of kinesin expression and type IV collagenase secretion in invasive human prostate PC-3 tumor sublines. Can Res 51: 5866–5875, 1991

    Google Scholar 

  80. Stephenson RA, Dinney CPN, Gohji K, Ordoney NG, Killion JJ, Fidler IJ: Metastatic model for human prostate cancer using orthotopic implantation in nude mice. J Natl Cancer Inst 84: 951–957, 1992

    Google Scholar 

  81. Jacobs SC, Pikna D, Lawson RK: Prostatic osteoblastic factor. Invest Urol 17: 195–198, 1979

    Google Scholar 

  82. Simpson E, Harrod J, Eilon G, Jacobs JW, Mundy GR: Identification of a messenger ribonucleic acid fraction in human prostatic cancer cells coding for a novel osteoblast-stimulating factor. Endocrinol 117: 1615–1620, 1985

    Google Scholar 

  83. Perkel VS, Subburaman M, Baylind DJ, Linkhart TA: An inhibitory insulin-like growth factor binding protein (INIGFBP) from human prostate cell conditioned medium reveals N-terminal sequence identity with bone-derived INIGFBP. J Clin Endoc and Metab 71: 533–535, 1990

    Google Scholar 

  84. Koutsilieris M, Rabbani SA, Goultzman D: Selective osteoblast mitogens can be extracted from prostatic tissue. Prostate 9: 109–115, 1986

    Google Scholar 

  85. Koutsilieris M, Rabbani SA, Bennet HP, Goultzman D: Characteristics of prostate derived growth factors for cells of the osteoblastic phenotype. J Clin Invest 80: 941–946, 1987

    Google Scholar 

  86. Gleave M, Hsich JT, Gao C, von Eschenbach AC, Chung WKL: Acceleration of human prostate cancer growthin vivo by factors produced by prostate and bone fibroblasts. Cancer Res 51: 3753–3761, 1991

    Google Scholar 

  87. Gleave ME, Hsich JT, von Eschenbach AC, Chung LWK: Prostate and bone fibroblasts induce human prostate cancer growthin vivo: implications for bidirectional tumor-stromal cell interactions in prostate carcinoma growth and metastasis. J Urol 147: 1151–1159, 1992

    Google Scholar 

  88. Camps JL, Chang SM, Hsu TC, Freeman MR, Hong SJ, Zhan HE, von Eschenbach AC, Chung LWK: Fibroblastmediated acceleration of human epithelial tumor growthin vivo. Proc Natl Acad Sci USA 87: 75–79, 1990

    Google Scholar 

  89. Chackel-Roy M, Niemeyer C, Moore M, Zetter BR: Stimulation of human prostatic carcinoma cell growth by factors present in human bone marrow. J Clin Invest 84: 43-, 1989

    Google Scholar 

  90. Hentter P, Vihko P: Growth factor regulation of gene expression in the human prostatic carcinoma cell line LNCaP. Cancer Res 53: 1051–1058, 1993

    Google Scholar 

  91. Donaldson JT, Tucker JA, Keane TE, Walther PJ, Webb KS: Characterization of a new model of human prostatic cancer: the multicellular tumor spheroid. Int J Cancer 46: 238–244, 1990

    Google Scholar 

  92. Perelson AS: Towards a realistic model of the immune system. pp. 377–401. In: Theoretical Immunology, Part II, Addison-Wesley, Redwood City, 1988

    Google Scholar 

  93. Mikulecky DC: Applications of network thermodynamics to problems in biomedical engineering. New York University Press, New York, 1993, pp 1–12

    Google Scholar 

  94. Hopfield JJ, Tank DW: Computing with neural circuits: A model. Science 233: 625–633, 1986

    Google Scholar 

  95. Prideaux JA, Mikulecky DC, Clarke A, Ware JL: A modified neural network model of tumor cell interactions and subpopulation dynamics. Invasion Metastasis, In Press

  96. Prideaux JP, Ware JL, Clark AM, Mikulecky DC: From neural networks to cell signalling: chemical communication in cell networks. J Biological Systems, Accepted, 1993

  97. Strom SC, Thompson MT, Brothman AR, Maygarden SJ, Collins SR, Bae VL, Ware JL: Immortalization of human prostate epithelial cells by transfection with SV40 large T antigen. Submitted, 1992

  98. Cussenot O, Berthon P, Berger R, Mowszowics I, Faille A, Hojman F, Teillac P, LeDay A, Calro F: Immortalization of human adult normal prostatic epithelial cells by liposomes containing large T-SV40 gene. J Urol 143: 881–886, 1991

    Google Scholar 

  99. Kaighn ME, Reddel RR, Lechner JF, Peehl DM, Camalier RF, Brash DE, Saffrotti, Harris C: Transformation of human neonatal prostate epithelial cells by strontrum phosphate transfection with a plasmid containing SV40 early region genes. Cancer Res 49: 3050–3065, 1989

    Google Scholar 

  100. Gingrich JR, Tucker JA, Walther PJ, Day JW, Poulton SHM, Webb KS: Establishment and characterization of a new human prostatic carcinoma cell line (DuPro-1). J Urol 146: 915–919, 1991

    Google Scholar 

  101. Webb KS, Keane TE, Yancey DR, Poulton SM, Walther PJ: The use of a mixed multicell tumor spheroid (MTS) model as an in vitro/in vivo model of prostate cancer. J Urol 147 (Abstract), 1992

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Ware, J.L. Growth factors and their receptors as determinants in the proliferation and metastasis of human prostate cancer. Cancer Metast Rev 12, 287–301 (1993). https://doi.org/10.1007/BF00665959

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