Interaction of androgen-induced autocrine heparin-binding growth factor with fibroblast growth factor receptor on androgen-dependent Shionogi carcinoma 115 cells.

Stimulation of a Shionogi carcinoma 115-derived cultured cell line (SC-3) with androgen resulted in secretion of heparin-binding growth factor. In this study, we analyzed cell-surfaced receptors for growth factors. Binding data of growth factors on intact SC-3 cells revealed the presence of low and high affinity receptors for epidermal growth factor (EGF), insulin, and fibroblast growth factor (FGF). The dissociation constant values were 50 pM and 1.0 nM for EGF, 1.2 nM and 30 nM for insulin, and 34 pM and 7.5 nM for FGF. The numbers of maximal binding sites were 300 and 900/cell for EGF, 2,000 and 14,000/cell for insulin, and 13,000 and 810,000/cell for FGF. To examine the association of androgen-induced growth factor with one of these receptors, the conditioned medium prepared from androgen-stimulated SC-3 cells was fractionated through a heparin-Sepharose column. Growth factor activity adsorbed and eluted by 1 M NaCl from the column was comigrated with the activity inhibiting FGF-receptor association. In addition, basic 125I-FGF was cross-linked, using disuccinimidyl suberate, to the receptor with an apparent molecular weight of 130,000, whose labeling was inhibited when basic FGF, acidic FGF, or highly purified androgen-induced growth factor was present in excess. Furthermore, the highly purified growth factor-, basic FGF- or androgen-induced growth of SC-3 cells was significantly and similarly inhibited by anti-basic FGF antibody IgG. These results indicate that androgen-induced FGF-like factor acts as an autocrine growth factor via the FGF receptor in a process of SC-3 cell proliferation.