EFFECT OF SURAMIN ON I-125-INSULIN-LIKE GROWTH FACTOR-I BINDING TO HUMAN MENINGIOMAS AND ON PROLIFERATION OF MENINGIOMA CELLS

Suramin, a polyanionic compound, has been shown to inhibit the binding of various growth factors to cell surface receptors. The effects of suramin on I-125-insulin-like growth factor (IGF)-I binding to human meningioma tissues and IGF-I-induced deoxyribonucleic acid (DNA) synthesis in cultured meningioma cells were examined using the quantitative receptor autoradiographic method and H-3-thymidine incorporation, respectively. Suramin inhibited specific I-125-IGF-I binding to meningioma tissue sections in a concentration-dependent manner, with a 50% inhibiting concentration (IC50) of 8.7 +/- 0.5 X 10(-5) M. The addition of 10(-3) M suramin to the incubation buffer potently dissociated I-125-IGF-I previously bound to meningioma tissue as a function of time (dissociation half-life (T-1/2) 6.8 minutes). After preincubation of tissue sections with 10(-3) M suramin for 120 minutes, there was no inhibition of the subsequent I-125-IGF-I binding to meningiomas. Suramin inhibited the IGF-I-induced incorporation of H-3-thymidine into meningioma cells in a dose-dependent manner, with an IC50 of 4.6 +/- 1.4 X 10(-5) M. The growth rate of meningioma cells (determined 4 days after seeding) was reduced by 10%, 20%, and 50% of the control culture in the presence of 10(-6), 10(-5), and 10(-4) M suramin, respectively. These results suggest that suramin interferes with IGF-I binding to meningioma tissue and inhibits proliferation of cells, at least partially by preventing IGF-I-induced DNA synthesis and probably by interacting with IGF-I directly rather than with its binding sites.