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

Ailiang Zeng; Zhiyun Wei; Rosalia Rabinovsky; Hyun Jung Jun; Rachid El Fatimy; Evgeny Deforzh; Ramil Arora; Yizheng Yao; Shun Yao; Wei Yan; Erik J. Uhlmann; Alain Charest; Yongping You; Anna M. Krichevsky

iScience (Aug 2020)

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

Ailiang Zeng,
Zhiyun Wei,
Rosalia Rabinovsky,
Hyun Jung Jun,
Rachid El Fatimy,
Evgeny Deforzh,
Ramil Arora,
Yizheng Yao,
Shun Yao,
Wei Yan,
Erik J. Uhlmann,
Alain Charest,
Yongping You,
Anna M. Krichevsky

Affiliations

Ailiang Zeng: Department of Neurology, 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
Zhiyun Wei: Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 201204, China; Corresponding author
Rosalia Rabinovsky: Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA
Hyun Jung Jun: Cancer Research Institute, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA
Rachid El Fatimy: Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA
Evgeny Deforzh: Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA
Ramil Arora: Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA
Yizheng Yao: Department of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA
Shun Yao: Department of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Center for Pituitary Tumor Surgery, Department of Neurosurgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510062, China
Wei Yan: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
Erik J. Uhlmann: Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA
Alain Charest: Cancer Research Institute, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
Yongping You: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
Anna M. Krichevsky: Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Corresponding author

Journal volume & issue: Vol. 23, no. 8
p. 101420

Abstract

Read online

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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

About the journal

Abstract

Keywords