Integrin involvement in glioblastoma multiforme: possible regulation by NF-kappa B

Glioblastoma multiforme (GBM) is the most malignant astroglial-derived rumo rs which has the propensity to aggressively infiltrate normal regions of th e brain surrounding the tumor. The interaction of tumor cells with the extr acellular matrix (ECM) is an integral step in the process of tumorigenesis and may play a role in the local invasion of the GBM cells. Our study inves tigated the role of the nuclear transcription factor NF-kappa B on GBM inte grin expression and cell attachment. Our results show that treatment of GBM cell lines, SNB-19 and T98G with PMA, an inducer of NF-kappa B, increased the expression of fibronectin and vitronectin genes. Accordingly, ectopic o ver-expression of NF kappa B subunits in GBM cells elevated the levels of f ibronectin gene expression, providing direct Evidence for a regulatory role for NF-kappa B in ECM protein production. Cell attachment to the ECM prote ins including fibronectin, vitronectin and laminin was increased in GBM and normal astrocytic cells. Interestingly, treatment of cells with PMA augmen ted attachment of SNB-19 and T98G cells to fibronectin and vitronectin, how ever it had no effect on attachment of normal astrocytes. Addition of the t ripeptide arginine-glycine-asparatic acid (RGD), the recognition site for m any integrins, significantly inhibited SNB-19 and T98G cell attachment to f ibronectin and vitronectin. Finally, activation of NF kappa B upon treatmen t of SNB cells with PMA led to an increase in the levels of mRNA for the be ta 3 and the alpha v integrin subunits. Collectively, these data demonstrat e a possible role for NF-kappa B in glioma cell attachment. J. Cell. Physio l. 184:214-221, 2000. (C) 2000 Wiley-Liss, Inc.