EphA2-mediatedM1-like polarization of microglia attenuatesglioblastoma metastasis

Background: EphA2 is upregulated in GBM tumor tissue specimens and established cancer cell lines and thought to be an attractive therapeutic target in cancer. We aim to define the role of EphA2 in polarization of microglia. Methods: Quantitative real-time polymerase chain reaction, immunofluorescence staining, and viral transfection-based knockdown and overexpression assays to assess the effect of EphA2 on microglia polarization. iTRAQ-LC-MS/MS and western blot were conducted to detect EphA2 and PI3K-Akt signaling activity. Using the Millicell system as an in vitro co-culture model, we performed transwell and western blot assays investigate the role of EphA2-mediated M1-like of microglia on GBM cells invasion and migration in vitro and in vivo . Results: In overexpressing and silencing experiments, we demonstrated that EphA2 contributed to the M1-like polarization of microglia. Mechanistically, PI3K-AKT signaling was the downstream of EphA2 and supported the process of EphA2 mediated the M1-like polarization of microglia. Finally, EphA2 mediated the M1-like polarization of microglia attenuated the migration and invasion ability of GBM cells in vitro and in vivo . Conclusions: Our study indicates that, distinct from its role on cancer cells, EphA2 promoted the M1-like polarization of microglia and further attenuated the metastasis of GBM.Our results provide a new information on rationale for targeting EphA2 to improve treatment outcomes in GBM patients.