EXTH-95. <i>In vivo</i> electrotaxis of glioblastoma in a rodent model

Abstract The treatment of glioblastoma (GBM) continues to be a major clinical challenge, in great part due to the diffusely invasive nature of tumor spread, including into the eloquent regions of the brain. This limits complete surgical resection, which contributes to the high rate of recurrence. Previously, the directional migration of GBM cells in response to direct current electrical fields (dcEFs), known as electrotaxis, had been observed and reported in vitro, with U87MG cells migrating towards the cathode. Here, we demonstrate for the first time, to the best of our knowledge, that dcEFs can guide GBM cell migration in vivo, offering a potentially transformative method to steer tumor invasion away from critical areas of the brain. In this study, rats were inoculated with U87MG-GFP+ cells and stimulated with pulsed dcEF continuously for 48 hours. We observed a significant and clinically meaningful cathodal shift and cathodal bias in the electrically stimulated group compared to the sham group (p = 0.0066; p &amp;lt; 0.0001, respectively). Notably, cathodal migration in vivo was achieved using lower applied dcEF than previously used in vitro, underscoring the feasibility of safely translating this technology to clinical settings. Furthermore, to elucidate the mechanisms underlying GBM electrotaxis, several proteins previously shown to be involved in mesenchymal and amoeboid cell migration were assessed via immunohistochemistry. The stimulated group showed an overexpression of ROCK1 and reduced expression of F-actin compared to the sham group (p = 0.0089; p =0.010, respectively) which is consistent with a shift toward amoeboid-based migration. Consequently, these findings demonstrate that dcEF induces directed migration of GBM cells in vivo, suggesting a paradigm-shifting therapeutic approach that could complement existing interventions by containing tumor spread or guiding the cells to resectable areas of the brain.