Upregulation of endothelin 1 and its precursor by IL-1 beta, TNF-alpha, and TGF-beta in the PC3 human prostate cancer cell line

Increasing evidence indicates that endothelin 1 (ET-1) is implicated in pro state tumour progression, However, data on ET-1 regulation in human prostat e and prostate cancer cell lines are lacking. In this study, regulation of ET-1 and its precursor big ET-1, using PC3 cells, a human bone metastatic p rostatic carcinoma cell line, was addressed, ET-1 and big ET-1 assays demon strated greater secretion of both peptides in the presence of 10% fetal cal f serum (FCS) as compared with 0.5% FCS, Incubation of PC3 cells in the abs ence and presence of various cytokines and growth factors known to be impli cated in prostate stroma-epithelium interactions, revealed that IL-6, FGF7/ KGF and FGF2/bFGF had no effect on ET-1 and big ET-1 secretion, whereas int erleukin 1 beta (IL-1 beta), tumour necrosis factor alpha (TNF-alpha) and t ransforming growth factor beta (TGF-beta) stimulated their secretion in a c oncentration-dependent manner. Binding experiments indicated the presence o f specific ET-1 receptors in PC3 cells: K-dapp = 1.1 +/- 0.2 X 10(-10) M, B -max = 2660 +/- 390 sites/cell. Data analysis demonstrated the presence of only the ETA receptor subtype in PC3 cells. In conclusion, our results indi cate that the implication of ET-1 in prostate cancer is likely to be mediat ed via paracrine/autocrine control of cell factors. (C) 1999 Academic Press .