Fibroblast Growth Factors And Their Receptors In Metastases Of Prostate And Other Urological Cancers

Zoran Culig, Marcus V. Cronauer, Alfred Hobisch, Georg Bartsch, and Helmut Klocker

Department of Urology, University of Innsbruck, Austria

Key words: Acid and basic fibroblast growth factor, prostate cancer, bladder cancer, renal cell carcinoma, invasion, metastasis, angiogenesis

Abstract: Theraputical options for advanced carcinoma of the prostate, bladder or kidney are limited. Therefore it is important to understand their invasion and metastasis, processes in which fibroblast growth factors play an important role. Basic fibroblast growth factor (bFGF) is expressed in androgen-insensitive prostate cancer cell lines PC-3 and DU-145 and in some clinical specimens. During progression of prostate cancer, the expression of the FGF receptor 2 isoform Illb, which preferentially binds keratinocyte growth factor (KGF) decreases and the expression of the isoform iiic, which preferentially binds bFGF increases. A similar phenomenon was observed in bladder cancer. Several FGFs are proposed to act as andromedins, proteins that mediate the effects of androgens in target tissues: FGF-7 (KGF), FGF-8 and FGF-10. In prostate and bladder cancer, FGFs regulate tumour metastases by induction of the matrix metalloproteinase promatrilysin. Matrix metalloproteinases degrade extracellular matrix proteins and their expression is elevated in prostate cancer cells. bFGF is strongly expressed in invasive bladder cancers in which it promotes angiogenesis. bFGF levels in bladder cancer are down-regulated by administration of interferon-alpha. bFGF and aFGF are frequently elevated in urine of bladder and renal cancer patients. There is a strong association between urinary bFGF and clinical parameters in bladder cancer. In renal cancer, it was shown that the transfection of bFGF cDNA leads to an increased invasiveness and formation of metastatic nodules.

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