Cell surface aggregation of elastin receptor molecules caused by suramin amplified signals leading to proliferation of human glioma cells

We have recently shown that glioma cell lines, as well as cells of human ma lignant gliomas in situ, synthesize tropoelastin. In addition, glioma cells degrade tropoelastin using metalloproteinase(s), and the resulting peptide s, incapable of assembling in the extracellular fibers, interact with the 6 7-kDa cell surface elastin binding protein (EBP), to transduce signals lead ing to up-regulation of cell proliferation. In this report, we show that ex posure to the polysulfonated bis-naphthylurea suramin causes accumulation o f physiologically active EBP molecules on the cell surface of a panel of gl ioma cell lines (U87, MG, U251 MG, U343 MG-A, U373 MG, SF 126, SF188, SF539 ), which results in an increase of cellular attachment to elastin-coated di shes and in an efficient binding of radiolabeled tropoelastin. Moreover, 10 0-200 mu M suramin stimulates [H-3]-thymidine incorporation by those surami n stimulates [3H]-thymidine incorporation by those tropoelastin-producing g lioma cell lines, but not by A 2058 melanoma cells, which do not produce el astin. Treatment of all glioma cell lines with 100 mu M suramin consistentl y increased expression of cyclin A and its cyclin-dependent kinase, cdk 2, to levels reached following the exposure to exogenous elastin-degradation p roducts (kappa-elastin). Our data suggest that a suramin-stimulated accumul ation of EBP molecules on the cell surface of glioma cells amplifies the el astin-derived signals, leading to their progression through the cell cycle.