Abstract 552: Microglia-stimulation of glioma cell invasion is dependent on EGFR and CSF1R signaling

Abstract

Abstract The ability of glioma tumor cells to invade surrounding brain parenchyma is what makes complete removal of tumor nearly impossible resulting in a median survival of only 12 months for patients afflicted by this disease. Targeting the motile properties of this tumor therefore, is an attractive strategy for therapeutic intervention. Many recent studies have demonstrated a key role for the tumor microenvironment in promoting tumor cell invasion and metastasis. Our laboratory and collaborators have demonstrated that tumor associated macrophages (TAMs) play a critical role in breast carcinoma invasion and metastasis. Here I propose a similar mechanism may occur between glioma cells and microglia within the brain. In this study we demonstrate that murine microglia are able to enhance GL261 glioma cell invasion into Matrigel in co-culture assays by up to 3 fold. Furthermore, we have found using pharmacological and/or antibody mediated inhibition of EGFR or CSF1R signaling abrogates this effect. GL261 cells constituitively secrete CSF-1, the levels of which are unaffected by EGF stimulation, EGFR inhibition or coculture with microglia. Disruption of EGF binding to EGFR using an EGF-specific function-blocking antibody also inhibits microglia-stimulated invasion, showing that EGF is responsible for mediating invasion. This data strongly suggests a paracrine loop exists between microglia and glioma similar to that seen in the breast cancer model. It is our hope that the results of this study may offer novel therapeutic approaches against glioblastoma by targeting functions of the tumor associated microglia as well as the glioma cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 552.