Abstract 46: Microglial stimulation of glioblastoma invasion involves EGFR and CSF-1R signaling

Abstract

Abstract The ability of glioma 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 glioma cell invasion. Coculture with microglia stimulates the invasion of GL261 glioma cells in-vitro. Pharmacological inhibition of EGFR using Iressa completely inhibits microglia-stimulated invasion and sequestration of EGF using an EGF-specific function-blocking antibody also fully inhibits microglia-stimulated glioma invasion. Furthermore, we demonstrate using novel CSF-1R (c-fms) inhibitors that CSF-1R signaling is also required for microglial enhancement of glioma 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. In addition, GL261 tumors orthotopically injected into the brains of C57 mice fed with PLX3397 were compromised in their ability to recruit microglia/macrophages. Interestingly, tumors from these animals also showed a 50% reduction in invasion into the parenchyma. These data indicate that during invasion, glioma and microglia cells signal to each other using EGF and CSF-1 similar to what has been observed in breast cancer models. The results of this study indicate the possibility of inhibiting glioblastoma invasion by targeting functions of tumor-associated microglia in addition to glioma cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 46. doi:1538-7445.AM2012-46