Glioblastoma Cell Migration is Directed by Electrical Signals

Abstract

Background:Electric field (EF) directed cell migration (electrotaxis) is known to occur in glioblastoma multiforme (GBM) and neural stem cells, with key signaling pathways frequently dysregulated in GBM. One such pathway is EGFR/PI3K/Akt, which is down-regulated by peroxisome proliferator activated receptor gamma (PPARγ) agonists. We investigated the effect of electric fields on GBM differentiated and stem cell migration and whether this was affected by treatment with the PPARγ agonist pioglitazone.MethodsPrimary GBM cell lines were cultured as differentiated and glioma stem cells (GSCs) and then exposed to EFs using electrotaxis chambers and imaged with time lapse microscopy. Cells were then treated with varying concentrations of pioglitazone and/or its inhibitor GW9662 and their responses to EFs examined.ResultsWe demonstrated that GBM differentiated and GSCs have opposing preferences for anodal and cathodal migration, respectively. Pioglitazone treatment resulted in significantly decreased directed cell migration in both cell types. Western blot analysis did not demonstrate any change in PPARγ expression with and without exposure to EF.ConclusionsOpposing EF responses in primary GBM differentiated cells and GSCs can be inhibited chemically by pioglitazone, implicating GBM EF modulation as a potential target in preventing tumour recurrence.