Heparin inhibits autocrine stimulation but not fibroblast growth factor stimulation of cell proliferation of androgen-responsive Shionogi carcinoma 115.
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 micrograms/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.
Kasayama
S
S
Third Department of Internal Medicine, Osaka University Hospital, Japan.
Sumitani
S
S
Tanaka
A
A
Yamanishi
H
H
Nakamura
N
N
Matsumoto
K
K
Sato
B
B
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D003470:Culture Media; D004273:DNA, Neoplasm / Q000096:biosynthesis; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D006133:Growth Substances / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology*; D013739:Testosterone / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D003470:Culture Media; D004273:DNA, Neoplasm; D006133:Growth Substances; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D013739:Testosterone; D005346:Fibroblast Growth Factors; D006493:Heparin