Journal
ISCIENCE
Volume 23, Issue 8, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.isci.2020.101420
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Funding
- NIH Common Fund [U19 CA179563]
- Office of Strategic Coordination/Office of the NIH [R21 NS098051, AG060019, R01 CA215072]
- National Natural Science Foundation of China
- [81901069]
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Glioblastoma (GBM) may arise from astrocytes through a multistep process involving a prow issive accumulation of mutations. We explored whether GBM-derived extracelblar 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-der ated 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 witt, EV-mediated transfer of full-length mRNAs encoding ribosomal proteins, oxidative phosphorylation, and glycolytic factors. Our study suggests an EV/extracerular RNA (exRNA)-mediated mechanism that contributes to astrocyte transformation via metabolic reprograming and implicates horizontal mRNA transfer.
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