EFFECTS OF GROWTH-FACTORS AND BASEMENT-MEMBRANE PROTEINS ON THE PHENOTYPE OF U-373 MG GLIOBLASTOMA CELLS AS DETERMINED BY THE EXPRESSION OFINTERMEDIATE FILAMENT PROTEINS

Various growth factors and basement membrane proteins have been implic ated in the pathobiology of astrocytomas, The goal of this study was t o determine the relative contribution of these two factors in modulati ng the phenotype of U-373 MG glioblastoma cells as determined by the e xpression of the intermediate filament proteins glial fibrillary acidi c protein, vimentin, and nestin, For these determinations, cells plate d in serum-free medium were treated either with growth factors binding to tyrosine kinase receptors including transforming growth factor-alp ha, epidermal growth factor, platelet-derived growth factor-AA, basic fibroblast growth factor, and insulin-like growth factor-1 or with bas ement membrane proteins including collagen IV, laminin, and fibronecti n, The changes in the expression levels of intermediate filament prote ins in response to these treatments were analyzed by quantitation of i mmunoblots, The results demonstrate that collagen IV and growth factor s binding to tyrosine kinase receptors decrease the glial fibrillary a cidic protein content of U-373 MG cells. Growth factors binding to tyr osine kinase receptors also decrease the vimentin content of these cel ls but do not affect their nestin content, On the other hand, basement membrane proteins decrease the nestin content of U-373 MG cells but d o not affect their vimentin content. The significance of these results with respect to the role played by different factors in modulating th e phenotype of neoplastic astrocytes during tumor progression is discu ssed.