Integrin involvement in Glioblastoma Multiforme: Possible regulation by NF-kappa B

Glioblastoma multiforme (GBM) is the most malignant astroglial-derived tumors which has the propensity to aggressively infiltrate normal regions of the brain surrounding the tumor. The interaction of tumor cells with the extracellular 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 investigated the role of the nuclear transcription factor NF-kappaB on GBM integrin expression and cell attachment. Our results show that treatment of GBM cell lines, SNB-19 and T98G with PMA, an inducer of NF-kappaB, increased the expression of fibronectin and vitronectin genes. Accordingly, ectopic over-expression of NFkappaB subunits in GBM cells elevated the levels of fibronectin gene expression, providing direct evidence for a regulatory role for NF-kappaB in ECM protein production. Cell attachment to the ECM proteins including fibronectin, vitronectin and laminin was increased in GBM and normal astrocytic cells. Interestingly, treatment of cells with PMA augmented attachment of SNB-19 and T98G cells to fibronectin and vitronectin, however it had no effect on attachment of normal astrocytes. Addition of the tripeptide arginine-glycine-asparatic acid (RGD), the recognition site for many integrins, significantly inhibited SNB-19 and T98G cell attachment to fibronectin and vitronectin. Finally, activation of NFkappaB upon treatment of SNB cells with PMA led to an increase in the levels of mRNA for the beta3 and the alphav integrin subunits. Collectively, these data demonstrate a possible role for NF-kappaB in glioma cell attachment.