Tumor cell plasticity, heterogeneity, and resistance in crucial microenvironmental niches in glioma

Abstract Both the perivascular niche (PVN) and integration into multicellular networks by tumor microtubes (TMs) have been associated with progression resistance to therapies in glioblastoma, but their specific contribution remained unknown. By long-term tracking of cell fate dynamics live mouse brain, differential therapeutic responses both niches are determined. PVN, a preferential location quiescent glioma cells, network facilitate against cytotoxic effects radiotherapy chemotherapy—independently each other, additive effects. Perivascular glioblastoma cells particularly able actively repair damage regions. Population PVN it depend on proficient NOTCH1 expression. In turn, downregulation induces resistant TM extension. Our findings identify as central switch between glioma, demonstrate robust cross-compensation when only one is targeted.