Expression And Function Of Fibroblast Growth Factors In Renal Cancer

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Renal cell carcinomas are characterized by hypervascularity, rapid metastasizing and poor prognosis. Therapeutical options for this malignancy are very limited. There was an interesting observation that human omental adipose tissue bFGF demonstrates greater angiogenic and mitogenic activity than either benign or cancerous tissue bFGF (75). It is known that renal cancer correlates with obesity, in particular in females (76).

bFGF cDNA-transfected renal cancer cell lines were more invasive than controls (77). Those cell lines also show an increased MMP-2 production and formed more than 10 times as many metastatic nodules in lungs as non-transfected or control cells. In that study, endogenous expression of bFGF fails to stimulate cell proliferation. bFGF was detected in conditioned media from the RC29 renal cancer cells which also respond to the exogenously added growth factor (78). Thus, at least some renal cancers might be stimulated by bFGF in an autocrine fashion. In human renal cancer cell cultures bFGF is inversely regulated to cell density (79).

The expression levels of bFGF in renal cancer mRNA and protein were higher than those measured in normal tissue (80). High bFGF levels were measured in kidney tumour tissue and in urine. The expression of bFGF in renal cell carcinoma and urinary bFGF inversely

References

1. Gospodarowicz D. Purification of a fibroblast growth factor from bovine pituitary. J Biol Chem 1975;250:2515-2520.

2. Böhlen P, Baird A, Esch F, Ling N, Gospodarowicz D. Isolation and partial molecular characterization of pituitary fibroblast growth factor. Proc Natl Acad Sci USA 1984;81:5364-5368.

3. Thomas KA, Rios-Cadelore M, Fitzpatrick S. Purification and characterization of acidic fibroblast growth factor from bovine brain. Proc Natl Acad Sci USA 1984;81:357-361.

4. Abraham JA, Whang JL, Tumolo A, Mergia A, Friedman J, Gospodarowicz D, Fiddes JC. Human basic fibroblast growth factor: nucleotide sequence and genomic organization. EMBO J 1986;5:2523-2528.

5. Gemel J, Gorry M, Ehrlich GD, MacArthur CA: Structure and sequence of human FGF8. Genomics 1996;35:253-257.

6. Miyamoto M, Naruo K, Seko C, Matsumoto S, Kondo T, Kurokawa T. Molecular cloning of a novel cytokine cDNA encoding the ninth member of the fibroblast growth factor family, which has a unique secretion property. Mol Cell Biol 1993; 13:4251-4259.

7. Beer HD, Florence C, Dammeier J, McGuire L, Werner S, Duan DR. Mouse fibroblast growth factor 10: cDNA cloning, protein characterization, and regulation of mRNA expression. Oncogene 1997;15:2211-2218.

correlated with patient survival (72,81). bFGF expression in the tumours is transient and dependent on the organ environment (82). Renal cell cancer metastatic cells were injected into the kidney or subcutis of nude mice. High vascularization was observed only in tumours injected into the kidney and urine of these animals contained higher bFGF levels.

The studies summarized in the present review show that FGFs are important for progression of urological cancers. A number of experimental therapies targeting angiogenesis is being developed and it is expected that these treatments could be evaluated in near future.

8. Partanen J, Makela TP, Eerola E, Korhonen J, Hirvonen H, Claesson-Welsh L, Alitalo K. FGFR-4, a novel acidic fibroblast growth factor receptor with a distinct expression pattern. EMBO J 1991;10:1347-1354.

9. Müller R, Bravo J, Burckhardt J. Induction of c-fos gene and protein by growth factors precedes activation of c-myc. Nature 1984;312:716-720.

10. Tsuda T, Hamamori Y, Yamashita T, Fukumoto Y, Takai Y. Involvement of three intracellular messenger systems, protein kinase C, calcium ion and cyclic AMP, in the regulation of c-fos gene. FEBS Lett 1986;208:39-42.

11. Tsuda T, Kaibuchi K, Kawahara Y, Fukuzaki H, Takai Y. Induction of protein kinase C activation and Ca2+ mobilization by fibroblast growth factor in Swiss 3T3 cells. FEBS Lett 1985;191:205-210.

12. Takeyama Y, Tanimoto T, Hoshijima M, Kaibuchi K, Ohyanagi H, Saitoh, Y, Takai Y. Enhancement of fibroblast growth factor-induced diacylglycerol formation and protein kinase C activation by colon tumour-promoting bile acid in Swiss 3T3 cells. Different modes of action between bile and phorbol ester. FEBS Lett 1986;197:339-343.

13. Abe K, Saito H. Neurotrophic effect of basic fibroblast growth factor is mediated by the p42/p44 mitogen-activated protein kinase cascade in cultured rat cortical neurons. Brain Res Dev Brain Res 2000;122:81-85.

14. Magnaldo I, L'Allemain G, Chambard JC, Moenner M, Barritault D, Pouyssegur J. The mitogenic signaling pathway of fibroblast growth factor is not mediated through phosphoinositide hydrolysis and protein kinase C activation in hamster fibroblasts. J Biol Chem 1986;261:16916-16922.

15. Kanda S, Hodgin MN, Woodfield RJ, Wakelam MJ. Thomas G. Claesson-Welsh L. Phosphatidylinositol 3* -kinase-independent

S6 kinase activation by fibroblast growth factor receptor-1 is important for proliferation but not differentiation of endothelial cells. J Biol Chem 1997;272:23347-23353.

16. Rifkin DB, Kojima S, Abe M, Harpel JG. TGF-beta: structure, function, and formation. Thromb Haemost 1993;70:177-179.

17. Gleave ME, Hsieh JT, Gao CA, von Eschenbach AC, Chung LW. Acceleration of human prostate cancer growth in vivo by factors produced by prostate and bone fibroblasts. Cancer Res 1991;51:3753-3761.

18. Gleave ME, Hsieh JT, von Eschenbach AC, Chung LWK. Prostate and bone fibroblasts induce human prostate cancer growth in vivo: implications for bidirectional tumour-stromal cell interaction in prostate carcinoma growth and metastasis. J Urol 1992;147:1151-1159.

19. Mansson PE, Adams P, Kan M, McKeehan WL. Heparin-binding growth factor gene expression and receptor characteristics in normal rat prostate and two transplantable rat prostatic tumours. Cancer Res 1989;49:2485-2494.

20. Sinowatz F, Amselgruber W, Lincoln D, Sasse J, Kolle S, Plendl J, Kayser K. Role of basic fibroblast growth factor in prostatic tumours. Nutrition 1995;11:619-621.

21. Hamaguchi A, Tooyama I, Yoshiki T, Kimura H. Demonstration of fibroblast growth factor receptor-1 in human prostate by polymerase chain reaction and immunohistochemistry. Prostate 1995;27:141-147.

22. Giri D, Ropiquet F, Ittman M. Alterations in expression of basic fibroblast growth factor (FGF) 2 and its receptor FGFR-1 in human prostate cancer. Clin Cancer Res 1999;5:1063-1071.

23. Story MT, Hopp KA, Molter M, Meier DA. Characteristics of FGF-receptors expressed by stromal and epithelial cells cultured from normal and hyperplastic prostates. Growth Factors 1994;10:269-280.

24. Yan G, Fukabori Y, MacBride G, Nikolaropoulous S, McKeehan WL. Exon switching and activation of stromal and embryonic fibroblast growth factor (FGF)-FGF receptor genes in prostate epithelial cells accompany stromal independence and malignancy. Mol Cell Biol 1993; 13:4513-4522.

25. Gao J, Isaacs JT. Development of an androgen receptor-null model for identifying the initiation site for androgen stimulation of proliferation and suppression of programmed (apoptotic) death of PC-82 human prostate cancer cells. Cancer Res 1998;58:3299-3306.

26. Olapade-Olaopa EO, MacKay EH, Taub NA, Sandhu DP, Terry TR, Habib FK. Malignant transformation of human prostatic epithelium is associated with the loss of androgen receptor immunoreactivity in the surrounding stroma. Clin Cancer Res 1999;5:569-576.

27. Carstens RP, Eaton JV, Krigman HR, Walther PJ, Garcia-Blanco MA. Alternative splicing of fibroblast growth factor receptor 2 (FGF-R2) in human prostate cancer. Oncogene 1997;15:3059-3065.

28. Nakamoto T, Chang CS, Li AK, Chodak GW. Basic fibroblast growth factor in human prostate cancer cells. Cancer Res 1992;52:571-577.

29. Feng S, Wang F, Matsubara A, Kan M, McKeehan WL. Fibroblast growth factor receptor 2 limits and receptor 1 accelerates tumourigenicity of prostate epithelial cells. Cancer Res 1997;57:5369-5378.

30. Matsubara A, Kan M, Feng S, McKeehan WL. Inhibition of growth of malignant rat prostate tumour cells by restoration of fibroblast growth factor receptor 2. Cancer Res 1998;58:1509-1514.

31. Dellacono F, Spiro J, Eisma R, Kreutzer D. Expression of basic fibroblast growth factor and its receptors by head and neck squamous carcinoma tumour and vascular endothelial cells. Am J Surg 1997;174:540-544.

32. Volm M, Koomagi R, Mattern J, Stammler G. Prognostic value of basic fibroblast growth factor and its receptor (FGFR-1) in patients with non-small cell lung carcinomas. Eur J Cancer 1997;33:691-693.

33. Cronauer MV, Hittmair A, Eder IE, Hobisch A, Culig Z, Ramoner R, Zhang J, Bartsch G, Reissigl A, Radmayr C, Thurnher M, Klocker H. Basic fibroblast growth factor levels in cancer cells and in sera of patients suffering from proliferative disorders of the prostate. Prostate 1997;31:223-33.

34. Hepburn PJ, Griffiths K, Harper ME. Angiogenic factors expressed by human prostatic cell lines: effect on endothelial cell growth in vitro. Prostate 1997;33:123-132.

35. Singh RK, Gutman M, Bucana CD, Sanchez R, Llansa N, Fidler IJ. Interferons alpha and beta down-regulate the expression of basic fibroblast growth factor in human carcinomas. Proc Natl Acad Sci USA 1995;92:4562-4566.

36. Dorkin TJ, Robinson MC, Marsh C, Neal DE, Leung HY. aFGF immunoreactivity in prostate cancer and its co-localization with bFGF and FGF8. J Pathol 1999;189:564-569.

37. Meyer GE, Yu E, Siegal JA, Petteway JC, Blumenstein BA, Brawer MK. Serum basic fibroblast growth factor in men with and without prostate carcinoma. Cancer 1995:76:2304-2311.

38. Ropiquet F, Berthon P, Villette JM, Le Brun G, Maitland NJ, Cussenot O, Fiet J. Constitutive expression of FGF2/bFGF in non-tumourigenic human prostatic epithelial cells results in the acquisition of a partial neoplastic phenotype. Int J Cancer 1997;72:543-547.

39. Marengo SR, Chung LW. An orthotopic model for the study of growth factors in the ventral prostate of the rat: effects of epidermal growth factor and basic fibroblast growth factor. J Androl 1994; 15:277-286.

40. Tanaka A, Furuya A, Yamasaki M, Hanai N, Kuriki K, Kamiakito T, Kobayashi Y, Yoshida H, Koike M, Fukayama M. High frequency of fibroblast growth factor (FGF) 8 expression in clinical prostate cancers and breast tissues, immunohistochemically demonstrated by a newly established neutralizing monoclonal antibody against FGF 8. Cancer Res 1998;58:2052-2056.

41. Dorkin TJ, Robinson MC, Marsh C, Bjartell A, Neal DE, Leung HY. FGF8 over-expression in prostate cancer is associated with decreased patient survival and persists in androgen independent disease. Oncogene 1999:18:27552761.

42. Culig Z, Hobisch A, Hittmair A, Peterziel H, Cato ACB, Bartsch G, Klocker H. Expression, structure, and function of androgen receptor in advanced prostatic carcinoma. Prostate 1998:35:63-70.

43. Wang Q, Stamp GW, Powell S, Abel P, Laniado M, Mahony C, Lalani EN, Waxman J. Correlation between androgen receptor expression and FGF8 mRNA levels in patients with prostate cancer and benign prostatic hypertrophy. J Clin Pathol 1999:52:29-34.

44. Yan G, Fukabori Y, Nikolaropoulos S, Wang F, McKeehan WL. Heparin-binding keratinocyte growth factor is a candidate stromal-to-epithelial-cell andromedin. Mol Endocrinol 1992:6:2123-2128.

45. Lu W, Luo Y, Kan M, McKeehan WL. Fibroblast growth factor-10. A second candidate to stromal to epithelial cell andromedin in prostate. J Biol Chem 1999;274:12827-12834.

46. De Bellis A, Crescioli C, Grappone C, Milani S, Ghiandi P, Forti G, Serio M. Expression and cellular localization of keratinocyte growth factor and its receptor in human hyperplastic prostate tissue. J Clin Endocrinol Metab 1998;83:2186-2191.

47. Nemeth JA, Zelner DJ, Lang S, Lee C. Keratinocyte growth factor in the rat ventral prostate: androgen-independent expression. J Endocrinol 1998;156:115-125.

48. Giri D, Ropiquet F, Ittmann M. FGF9 is an autocrine and paracrine prostatic growth factor expressed by prostatic stromal cells. J Cell Physiol 1999:180:53-60.

49. Klein RD, Maliner-Jongewaard MS, Udayakumar TS, Boyd JL, Nagle RB, Bowden GT. Promatrilysin expression is induced by fibroblast growth factors in the prostatic carcinoma cell line LNCaP but not in normal primary prostate epithelial cells. Prostate 1999:41:215-223.

50. Pajouh MS, Nagle RB, Breathnach R, Finch JS, Brawer MK, Bowden GT. Expression of metalloproteinase genes in human prostate cancer. J Cancer Res Clin Oncol 1991; 117:144150.

51. Pienta KJ, Isaacs WB, Vindivich D, Coffey DS. The effects of basic fibroblast growth factor and suramin on cell motility and growth of rat prostate cancer cells. J Urol 1991:145:199-202.

52. Hrzenjak M, Shain SA. Fibroblast growth factor-2 and TPA enhance prostate cancer cell proliferation and activate members of the ras and PKC signal transduction pathways. Recept Signal Tranduct 1997:7:207-219.

53. Cronauer MV, Nessler-Menardi C, Klocker H, Maly K, Hobisch A, Bartsch G, Culig Z. Androgen receptor protein is down-regulated by basic fibroblast growth factor in prostate cancer cells. Br J Cancer 2000:82:39-45.

54. Gong Y, Blok LJ, Perry JE, Lindzey JK, Tindall DJ. Calcium regulation of androgen receptor expression in the human prostate cancer cell line LNCaP. Endocrinology 1995:136:2172-2178.

55. O'Brien T, Cranston D, Fuggle S, Bicknell R, Harris AL. Two mechanisms of basic fibroblast growth factor-induced angiogenesis in bladder cancer. Cancer Res 1997:57:136-140.

56. Allen LE, Maher PA. Expression of basic fibroblast growth factor and its receptor in an invasive bladder carcinoma cell line. J Cell Physiol 1993:155:368-375.

57. Miyake H, Yoshimura K, Hara I, Eto H, Arakawa S, Kamidono S. Basic fibroblast growth factor regulates matrix metalloproteinases production and in vitro invasiveness in human bladder cancer cell lines. J Urol 1997;157:2351-2355.

58. De Boer WI, Vermeij M, Gil Diez de Medina S, Bindels E, Radvanyi F, van der Kwast T, Chopin D. Functions of fibroblast and transforming growth factors in primary organoid-like cultures of normal human urothelium. Lab Invest 1996;75:147-156.

59. Davies B, Waxman J, Wasan H, Abel P, Williams G, Krausz T, Neal D, Thomas D, Hanby A, Balkwill F. Levels of matrix metalloproteases in bladder cancer correlate with tumour grade and invasion. Cancer Res 1993;53:5365-5369.

60. Jouanneau J, Plouet J, Moens G, Thiery JP. FGF-2 and FGF-1 expressed in rat bladder carcinoma cells have similar angiogenic potential but different tumourigenic properties in vivo. Oncogene 1997;14:671-676.

61. Jouanneau J, Moens G, Montesano R, Thiery JP. FGF-1 but not FGF-4 secreted by carcinoma cells promotes in vitro and in vivo angiogenesis and rapid tumour proliferation. Growth Factors 1995;12:37-47.

62. Jouanneau J, Moens G, Bourgeois Y, Poupon MF, Thiery JP. A minority of carcinoma cells producing acidic fibroblast growth factor induces a community effect for tumour progression. Proc Natl Acad Sci USA 1994;91:286-290.

63. Okada-Ban M, Moens G, Thiery JP, Jouanneau J. Nuclear 24 kD fibroblast growth factor (FGF)-2 confers metastatic properties on rat bladder carcinoma cells. 1999.

64. Dinney CPN, Bielenberg DR, Perrotte P, Reich R, Eve BY, Bucana CD, Fidler IJ. Inhibition of basic fibroblast growth factor expression, angiogenesis, and growth of human bladder carcinoma in mice by systemic interferon-alpha administration. Cancer Res 1998;58:808-814.

65. Slaton JW, Perrotte P, Inoue K, Dinney CP, Fidler IJ. Interferon-alpha-mediated down-regulation of angiogenesis-related genes and therapy of bladder cancer are dependent on optimization of biological dose and schedule. Clin Cancer Res 1999;5:2726-2734.

66. Campbell SC, Volpert OV, Ivanovich M, Bouck NP. Molecular mediators of angiogenesis in bladder cancer. Cancer Res 1998;58:1298-1304.

67. De Boer WI, Houtsmuller AB, Izadifar V, Muscatelli-Groux B, van der Kwast TH, Chopin DK.. Expression and functions of EGF. FGF and family members and their receptors in invasive human transitional-cell-carcinoma cells. Int J Cancer 1997;71:284-291.

68. Diez de Medina SG, Chopin D, El Marjou A, Delouvee A, LaRochelle WJ, Hoznek A, Abbou C, Aaronson SA, Thiery JP, Radvanyi F. Decreased expression of keratinocyte growth factor receptor in a subset of human transitional cell bladder carcinomas. Oncogene 1997;14:323-330.

69. Chodak GW, Hospelhorn V, Judge SM, Mayforth R, Koeppen H, Sasse J. Increased levels of flbroblast growth factor-like activity in urine from patients with bladder or kidney cancer. Cancer Res 1988;48:2083-2088.

70. O'Brien T, Smith K, Cranston D, Fuggle S, Bicknell R, Harris A. Urinary basic flbroblast growth factor is elevated in patients with bladder cancer and benign prostate hypertrophy. Br J Urol 1995;76:311-314.

71. Nguyen M, Watanabe H, Budson AE, Richie JP, Folkman J. Elevated levels of the angiogenic peptide basic flbroblast growth factor in urine of bladder cancer patients. J Natl Cancer Inst 1993;85:241-242.

72. Nguyen M, Watanabe H, Budson AE, Richie JP, Hayes DF, Folkman J. Elevated levels of an angiogenic peptide, basic flbroblast growth factor, in the urine of patients with a wide spectrum of cancers. J Natl Cancer Inst 1994;86:356-361.

73. Chopin DK, Caruelle JP, Colombel M, Palcy S, Ravery V, Caruelle D, Abbou CC, Barritault D. Increased immunodetection of acidic flbroblast growth factor in bladder cancer, detectable in urine. J Urol 1993;150:1126-1130.

74. Valles AM, Boyer B, Badet J, Tucker GC, Barritault D, Thiery JP. Acidic flbroblast growth factor is a modulator of epithelial plasticity in a rat bladder carcinoma cell line. Proc Natl Acad Sci USA 1990;87:1124-1128.

75. Mydlo JH, Kral JG, Macchia RJ. Preliminary results comparing the recovery of basic flbroblast growth factor (FGF-2) in adipose tissue and benign and malignant renal tissue. J Urol 1998; 159:2159-2163.

76. Chow WH, Mclaughlin JK, Mandel JS, Wacholder S, Niwa S, Fraumeni JFJ. Obesity and risk of renal cell cancer. Cacer Epidemiol Biomark Prevent 1996;5:17-21.

77. Miyake H, Hara I, Yoshimura K, Eto H, Arakawa S, Wada S, Chihara K, Kamidono S. Introduction of basic flbroblast growth factor gene into mouse renal cell carcinoma enhances its metastatic potential. Cancer Res 1996;56:2440-2445.

78. Mydlo JH, Zajac J, Macchia RJ. Conditioned media from a renal cell carcinoma cell line demonstrates the presence of basic fibroblast growth factor. J Urol 1993; 150:997-1001.

79. Singh RK, Llansa N, Bucana CD, Sanchez R, Koura A, Fidler IJ. Cell density-dependent regulation of basic fibroblast growth factor expression in human renal cell carcinoma cells. Cell Growth Differ 1996;7:397-404.

80. Eguchi J, Nomata K, Kanda S, Igawa T, Taide M, Koga S, Matsuya F, Kanetake H, Saito Y. Gene expression and immunohistochemical localization of basic fibroblast growth factor in renal cell carcinoma. Biochem Biophys Res Commun 1992;183:937-944.

81. Nanus DM, Schmitz-Drager BJ, Motzer RJ, Lee AC, Vlamis V, Cordon-Cardo C, Albino AP, Reuter VE. Expression of basic fibroblast growth factor in primary human renal tumours: correlation with poor survival. J Natl Cancer Inst 1994;85:1597-1599.

82. Singh RK, Bucana CD, Gutman M, Fan D, Wilson MR, Fidler IJ. Organ site-dependent expression of basic fibroblast growth factor in human renal cell carcinoma cells. Am J Pathology 1994;145:365-374.

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