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 aggressive behavior, we examined hyaluronate-CD44 signaling. CD44, a hyaluronate receptor, is known to be highly expressed in glioma and its expression showed good correlation with invasiveness of the tumor. Treatment of glioma cells with hyaluronate activated rapid and transient tyrosine phosphorylation of several proteins including p125(FAK), while neuroblastoma cells that express no detectable CD44 had no response to the treatment. This hyaluronate-dependent tyrosine phosphorylation was blocked by anti-CD44 antibody, suggesting its direct mediation by CD44. Moreover, we found that hyaluronate-treatment activated mitogen activated protein (MAP) kinase. These results strongly suggest that hyaluronate-CD44 signaling may play a role in tumor invasion and proliferation by activation of p125(FAK) and MAP kinase in human glioma cells.