PROLIFERATION OF CULTURED HUMAN PROSTATE-CANCER CELLS IS INHIBITED BYINSULIN-LIKE GROWTH-FACTOR (IGF) BINDING PROTEIN-1 - EVIDENCE FOR AN IGF-II AUTOCRINE GROWTH LOOP

In this study, we examined the expression of insulin-like growth facto r (IGF) ligands, receptors (IGFR(1), IGFR(2)), and binding proteins (I GFBPs) in the human prostate cancer cell line DU145, as well as its mi togenic response to the IGFs. Using RNase protection assays, we found expression of IGF-II, IGFR(1), and IGFR(2) but failed to detect IGF-I messenger RNA. Distinct binding protein species as well as immunoreact ive IGF-II were detected in conditioned media using radioligand and im munoblotting assays. Compared with controls, treatment with exogenous IGF-I and IGF-II resulted in stimulation of monolayer and anchorage-in dependent growth. Recombinant human IGFBP-1, which binds IGF-II with h igh affinity, inhibited IGF-II-induced monolayer growth and both basel ine and IGF-II-induced anchorage-independent growth in this cell line. Our data suggest IGF-II is as an autocrine growth factor in DU145 cel ls, and that inhibition of IGF-II-dependent growth of human prostate c ancer cells may represent a new therapeutic strategy for this disease.