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 malignant gliomas in situ, synthesize tropoelastin. In addition, glioma cells degrade tropoelastin using metalloproteinase(s), and the resulting peptides, incapable of assembling in the extracellular fibers, interact with the 67-kDa cell surface elastin binding protein (EBP), to transduce signals leading to up-regulation of cell proliferation. In this report, we show that exposure to the polysulfonated bis-naphthylurea suramin causes accumulation of physiologically active EBP molecules on the cell surface of a panel of glioma 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 dishes and in an efficient binding of radiolabeled tropoelastin. Moreover, 100-200 microM suramin stimulates [3H]-thymidine incorporation by those tropoelastin-producing glioma cell lines, but not by A 2058 melanoma cells, which do not produce elastin. Treatment of all glioma cell lines with 100 microM suramin consistently increased expression of cyclin A and its cyclin-dependent kinase, cdk 2, to levels reached following the exposure to exogenous elastin-degradation products (kappa-elastin). Our data suggest that a suramin-stimulated accumulation of EBP molecules on the cell surface of glioma cells amplifies the elastin-derived signals, leading to their progression through the cell cycle.
Hinek
A
A
Cardiovascular Research, The Hospital for Sick Children, Toronto, Ontario, Canada.
Jung
S
S
Rutka
J T
JT
D002455:Cell Division / Q000187:drug effects; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004549:Elastin / Q000494:pharmacology; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013498:Suramin / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D014316:Tritium; D014333:Tropoelastin / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects
D016895:Culture Media, Serum-Free; D016213:Cyclins; D007797:Laminin; D011956:Receptors, Cell Surface; D014333:Tropoelastin; C054901:elastin-binding proteins; D014316:Tritium; D013498:Suramin; D004549:Elastin; D018844:Cyclin-Dependent Kinases; D013936:Thymidine