ME-09 * DYNAMIC EVIDENCE OF TUMOR INDUCED MICROGLIA ACTIVATION AT THE INFILTRATIVE MARGINS OF GLIOMA

Abstract

PURPOSE: Microglia are a major cellular component of malignant glioma, and in some cases, compose up to 40% of the mass of the tumor. Previous studies have shown that microglia can decrease T-cell response to glioma, and their abundance is correlated with increased histologic grade. These studies suggest that microglia facilitate the progression and infiltration of glioma, however the dynamics of the relationship between tumor cells and microglia are not well characterized. METHODS: In this work, we examined the dynamic migratory behavior of glioma and microglia cells using two-color time-lapse fluorescence microscopy of brain slices from a PDGF-driven rat model of glioma in which glioma cells and microglia were labeled with separate fluorescent markers. We quantified glioma cells and microglia motility through single cell tracking and particle image velocimetry. RESULTS: We found that microglia were predominately abundant within the tumor mass and that microglia motility was strongly correlated with the presence of glioma cells. This provides the first dynamic evidence that glioma induces microglial motility. We found that motility of glioma cells and microglia were variably correlated. Our results also show that microglia and glioma cells exhibit stark differences in migratory behavior. Microglia move by a simple random walk, while glioma cells exhibit highly persistent motion, characterized as super diffusion, within the same microenvironment indicating intrinsic differences in response to migratory cues. CONCLUSION: These results provide the first dynamic evidence of glioma cells stimulating the activation of microglia, by means of increasing motility and localization in and around the infiltrative edge of glioma. Further, these results show dynamic interactions between glioma and microglia and suggest that glioma cells and microglia are either responding to different migratory cues, or are responding to the same cues in different ways.