TPA-MEDIATED REGULATION OF OSTEOPONTIN IN HUMAN-MALIGNANT GLIOMA-CELLS

Malignant gliomas are the most common primary intracranial neoplasms i n adults and ave largely refractory to post-surgical therapy despite i ntensive therapeutic efforts. Using a number of different brain tumor- derived cell lines we have demonstrated that the mRNA for osteopontin (OPN), which is substantially over-expressed by some tumors in compari son with normal tissues, is preferentially expressed in high grade and metastatic brain tumors compared to low grade brain tumors. One gliom a-derived cell line, U105MG, which does not express significant amount s of OPN mRNA, could be induced dose-dependently by the tumor promotin g and PKC-activating phorbol ester, TPA, to over-express OPN mRNA in a PKC-dependent manner. Unexpectedly, treatment of U105MG cells Ca2+ io nophore (A23187) completely inhibited TPA mediated induction of OPN wh ile treatment with the intracellular Ca2+ antagonist TMB-8 had no sign ificant effect. Elucidation of regulatory mechanisms for OPN induction in glioma cells should facilitate rational design of novel therapeuti cs for human malignant gliomas.