TMIC-07. PYK2 SIGNALING IS UPREGULATED IN RECURRENT GLIOBLASTOMA TUMORS IN C57BL/6/GL261 GLIOMA IMPLANTATION MODEL

Abstract

Abstract Glioblastoma (GBM) is the most aggressive type of brain cancer with no successful treatment available. Microglia makes up to 30% of total GBM tumor mass. Previously we demonstrated that microglia within the tumor stimulate glioma cell growth and invasion through the proline rich tyrosine kinase 2 (Pyk2). Tumor resection is the first line treatment for GBM. Our previous studies with use of mouse glioma implantation model indicate that microglia in a site of tumor resection undergo significant modulations in cytokines expression profile. We hypothesize that microglia activated by tumor resection induces Pyk2 signaling in glioma cell and promotes malignant properties of the tumor cells that fail to be eliminated by resection. Using C57BL/6/GL261 mouse glioma implantation model, we analyzed primary implanted tumors and re-grown tumor after surgical resection. Two weeks after glioma cells implantation, tumor resection was performed, and two weeks later regrown tumors were used for western blot analysis. Total Pyk2 and phosphorylated Pyk2[Y579/50] were analyzed. The study revealed that Pyk2 phosphorylation is upregulated in re-grown tumor compared to primary implanted tumor. Treatment with PF-562271 (Pyk2/FAK inhibitor, once/daily, 50mg/kg, orally) beginning the 2ndday after tumor resection, reduced Pyk2 phosphorylation in regrown tumors compared to animals that did not receive treatment with PF-562271. In conclusion we can state that tumor resection procedure induces the upregulation of Pyk2 phosphorylation in regrown tumors. This effect is eliminated with oral administration of PF-562271.