Research ArticleBRAIN TUMOR

Wnt-mediated endothelial transformation into mesenchymal stem cell–like cells induces chemoresistance in glioblastoma

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Science Translational Medicine  26 Feb 2020:
Vol. 12, Issue 532, eaay7522
DOI: 10.1126/scitranslmed.aay7522

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Endothelial transformation in glioblastoma

Glioblastoma (GBM) is one of the most aggressive brain tumors. GBM is characterized by resistance to cytotoxic therapies and extensive vascular abnormalities. It has been recently shown that GBM-associated endothelial cells (ECs) might play a role in GBM cytotoxic resistance. Now, Huang et al. used in vitro cell cultures and in vivo models to investigate the role of ECs in pharmacoresistance. The authors showed that GBM-associated ECs acquired a mesenchymal stem cell–like phenotype, driving tumor resistance. Mesenchymal transformation was triggered by Wnt/β-catenin signaling activation in ECs. In a mouse model, β-catenin inhibition sensitized GBM to cytotoxic treatment, suggesting that combining cytotoxic therapy with Wnt signaling inhibition might overcome pharmacoresistance in GBM.

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