Heparin inhibits autocrine stimulation but not fibroblast growth factor stimulation of cell proliferation of androgen-responsive shionogi carcinoma 115

Abstract

An androgen‐responsive cloned cell line (SC‐3) derived from Shionogi carcinoma 115 (SC115) has been shown to secrete fibroblast growth factor (FGF)‐like peptide in response to androgen, which binds to FGF receptor and promotes the proliferation of SC‐3 cells in an autocrine mechanism. Since the androgen‐induced autocrine factor has a property to bind heparin, we examined the effects of heparin on the growth of SC‐3 cells. Heparin was found to exhibit significant inhibition of testosterone‐induced growth in a concentration‐dependent manner: Approximately 50% inhibition was found at a concentration of 0.1 μg/ml. DNA synthesis of SC‐3 cells induced by testosterone was also inhibited strongly by heparin, and less strongly by heparan sulfate and dermatan sulfate. Proliferation of SC‐3 cells induced by acidic (a) or basic (b) FGF appeared not to be modulated by heparin. In contrast, heparin efficiently blocked DNA synthesis stimulated with androgen‐induced growth factor in the conditioned medium from testosterone‐treated cells. These results indicate that heparin inhibits autocrine loop in SC‐3 cells induced by androgen. Thus the autocrine growth factor possesses a different characteristic from aFGF and bFGF in that its bioactivities are negatively modulated by the glycosaminoglycan.