HYALURONATE ACTIVATES TYROSINE PHOSPHORYLATION OF CELLULAR PROTEINS INCLUDING FOCAL ADHESION KINASE VIA CD44 IN HUMAN GLIOMA-CELLS

To search for the signaling pathway of glioma cells relevant to its ag gressive behavior, we examined hyaluronate-CD44 signaling. CD44, a hya luronate receptor, is known to be highly expressed in glioma and its e xpression showed good correlation with invasiveness of the tumor. Trea tment of glioma cells with hyaluronate activated rapid and transient t yrosine phosphorylation of several proteins including p125(FAK), while neuroblastoma cells that express no detectable CD44 had no response t o the treatment. This hyaluronate-dependent tyrosine phosphorylation w as blocked by anti-CD44 antibody, suggesting its direct mediation by C D44. Moreover, we found that hyaluronate-treatment activated mitogen a ctivated protein (MAP) kinase. These results strongly suggest that hya luronate-CD44 signaling may play a role in tumor invasion and prolifer ation by activation of p125(FAK) and MAP kinase in human glioma cells.