FIBRONECTIN-MEDIATED CELL-MIGRATION PROMOTES GLIOMA CELL INVASION THROUGH CHEMOKINETIC ACTIVITY

In order to investigate the biological role of fibronectin in glioma c ell invasion, we studied the relation between migratory responses or a dhesiveness of glioma cells to fibronectin and the in vitro Invasion i n three human malignant glioma cell lines, A172, T98G and U373MG. All these cell lines chemotactically migrated in a dose-dependent manner t o fibronectin in concentrations ranging from 0.5 to 10 mu g/ml, with A 172 cells showing the strongest migration and U373 cells the weakest. Checkerboard analyses demonstrated that A172 and T98G cells showed muc h stronger chemokinetic responses to fibronectin than U373MG cells. In contrast to the migratory responses, A172 and U373MG cells showed an almost equally high adhesion to fibronectin and T98G cells a low adhes ion. The degree of expression of the integrin alpha 5 subunit correlat ed,yell with the strength of glioma cell adhesion to fibronectin rathe r than that of migration to the molecule. Furthermore, the cell adhesi on to fibronectin was almost completely inhibited by arginine-glycine- aspartic acid (RGD)containing peptides, but the fibronectin-stimulated cell migration was only partially inhibited. An in vitro invasion ass ay disclosed that U373MG cells invaded the artificial basement membran e barrier the most and A172 cells the least. However, addition of fibr onectin to the glioma cells markedly enhanced the invasive activity of A172 and T98G cells but had little effect on that of U373MG cells. Th ese results indicate that fibronectin-stimulated migration can be one of the factors promoting invasiveness of glioma cells and that the che mokinetic activity of fibronectin may play a crucial role in glioma in vasion through conferring motor-driving force on the glioma cells.