Abstract 3110: Microglia-stimulation of glioma cell invasion is dependent on EGFR and CSF1R signaling

Abstract

Abstract Glioblastoma multiforme is a deadly cancer whose current treatment options are limited. The ability of glioblastoma tumor cells to infiltrate the surrounding brain parenchyma makes complete removal of these tumors nearly impossible. We investigated how microglia, the resident macrophages of the brain, stimulate glioblastoma cell invasion. We examined the ability of normal microglia from C57Bl/6J mice to stimulate GL261 glioblastoma cell invasion in vitro. The two cell populations were differentially labeled with cell tracker dyes and invasion was quantified by confocal imaging. The effect of inhibiting EGFR and CSF1R (c-fms) on microglia-stimulated glioblastoma invasion using pharmacological agents was tested. We also determined the level of EGF and CSF1 ligand expression by glioblastoma and microglial cells using ELISA, western blotting, and immunofluorescence. We found that microglia stimulate the invasion of GL261 glioblastoma cells by approximately 8 fold in an in vitro invasion assay. Pharmacological inhibition of EGFR strongly inhibited microglia-stimulated invasion. Furthermore, using a pharmacological CSF-1R kinase domain inhibitor, we showed that CSF-1R signaling is also required for microglial enhancement of glioblastoma invasion. GL261 cells were found to constitutively secrete CSF-1, the levels of which are unaffected by EGF stimulation, EGFR inhibition or coculture with microglia. We also demonstrated that microglia express EGF which is largely associated with the plasma membrane. These data indicate that during invasion, glioblastoma and microglia cells signal to each other using EGF and CSF-1. The results of this study indicate the possibility of inhibiting glioblastoma invasion by targeting glioblastoma-associated microglia. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3110. doi:10.1158/1538-7445.AM2011-3110