Glioma Cell Migration on Three-dimensional Nanofiber Scaffolds Is Regulated by Substrate Topography and Abolished by Inhibition of STAT3 Signaling

摘要: A hallmark of malignant gliomas is their ability to disperse through neural tissue, leading long-term failure all known therapies. Identifying new antimigratory targets could reduce glioma recurrence and improve therapeutic efficacy, but screens based on conventional migration assays are hampered by the limited these reproduce native cell motility. Here, we have analyzed motility, gene expression, sensitivity inhibitors cells cultured scaffolds formed submicron-sized fibers (nanofibers) mimicking topography. Glioma aligned nanofiber reproduced elongated morphology migrating in white matter tissue were highly sensitive myosin II inhibition only moderately affected stress fiber disruption. In contrast, same displayed a flat opposite actin when culture polystyrene. Gene expression analysis indicated correlation between nanofibers increased STAT3 signaling, driver progression. Accordingly, out glioblastoma-derived neurospheres tumor explants was reduced at subtoxic concentrations. Remarkably, ineffective tested concentrations two-dimensional assay. We conclude that regulated topographical cues affect adhesion expression. Cell using be used mechanisms identify strategies not disclosed other vitro models.