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

iScience

Yongping You¹  Hyun Jung Jun²  Rachid El Fatimy³  Zhiyun Wei⁴  Ramil Arora⁵  Ailiang Zeng⁶  Wei Yan⁶  Evgeny Deforzh⁶  Rosalia Rabinovsky⁶  Yizheng Yao⁶  Shun Yao⁶  Erik J. Uhlmann⁷  Alain Charest⁷  Anna M. Krichevsky⁸ 

[1] Center for Pituitary Tumor Surgery, Department of Neurosurgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510062, China;Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 201204, China;Corresponding author;Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China;Cancer Research Institute, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA;Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA;Department of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA;Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China;

关键词: Biological Sciences;    Cell Biology;    Cancer;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: 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.

【 授权许可】

Unknown