Glioblastoma-Derived Extracellular Vesicles Facilitate Transformation of Astrocytes via Reprogramming Oncogenic Metabolism

• Published in: iScience Vol. 23; no. 8; p. 101420
• Main Authors: Zeng, Ailiang, Wei, Zhiyun, Rabinovsky, Rosalia, Jun, Hyun Jung, El Fatimy, Rachid, Deforzh, Evgeny, Arora, Ramil, Yao, Yizheng, Yao, Shun, Yan, Wei, Uhlmann, Erik J., Charest, Alain, You, Yongping, Krichevsky, Anna M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21-08-2020; Elsevier
• Subjects: Biological Sciences; Cancer; Cell Biology; Biological Sciences; Cell Biology; Cancer
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2020.101420

Glioblastoma (GBM) may arise from astrocytes through a multistep process involving a progressive accumulation of mutations. We explored whether GBM-derived extracellular vesicles (EVs) may facilitate neoplastic transformation and malignant growth of astrocytes. We utilized conditioned media (CM) of cultured glioma cells, its sequential filtration, diverse cell-based assays, RNA sequencing, and metabolic assays to compare the effects of EV-containing and EV-depleted CM. GBM EVs facilitated the neoplastic growth of pre-transformed astrocytes but not normal human or mouse astrocytes. They induced proliferation, self-renewal, and colony formation of pre-transformed astrocytes and enhanced astrocytoma growth in a mouse allograft model. GBM EVs appear to reprogram astrocyte metabolism by inducing a shift in gene expression that may be partly associated with EV-mediated transfer of full-length mRNAs encoding ribosomal proteins, oxidative phosphorylation, and glycolytic factors. Our study suggests an EV/extracellular RNA (exRNA)-mediated mechanism that contributes to astrocyte transformation via metabolic reprograming and implicates horizontal mRNA transfer.
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•Extracellular vesicles (EVs) shed by glioma cells are taken up by astrocytes•Glioma EVs facilitate astrocyte transformation and tumor growth•EVs reprogram glycolysis and oxidative phosphorylation of transformed astrocytes•mRNAs coding ribosomal proteins and other factors are dispersed via EVs
Biological Sciences; Cell Biology; Cancer