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

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Output type: Journal article

UM6P affiliated Publication?: Yes

Author list: Zeng A., Wei Z., Rabinovsky R., Jun H.J., El Fatimy R., Deforzh E., Arora R., Yao Y., Yao S., Yan W., Uhlmann E.J., Charest A., You Y., Krichevsky A.M.

Publication year: 2020

Journal: iScience

Volume number: 23

Issue number: 8

eISSN: 2589-0042

URL: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85089186716&origin=inward

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Abstract

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.

Keywords

Biological Sciences, Cell Biology

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