Phenotype and neuronal cytotoxic function of glioblastoma extracellular vesicles

Zhou, W. et al. (2022) Phenotype and neuronal cytotoxic function of glioblastoma extracellular vesicles. Biomedicines, 10(11), 2718. (doi: 10.3390/biomedicines10112718) (PMID:36359238) (PMCID:PMC9688005)

Abstract

Glioblastoma (GBM) is the most aggressive and lethal form of brain tumor. Extracellular vesicles (EVs) released by tumor cells play a critical role in cellular communication in the tumor microenvironment promoting tumor progression and invasion. We hypothesized that GBM EVs possess unique characteristics which exert effects on endogenous CNS cells including neurons, producing dose-dependent neuronal cytotoxicity. We purified EVs from the plasma of 20 GBM patients, 20 meningioma patients, and 21 healthy controls, and characterized EV phenotypes by electron microscopy, nanoparticle tracking analysis, protein concentration, and proteomics. We evaluated GBM EV functions by determining their cytotoxicity in primary neurons and the neuroblastoma cell line SH-SY5Y. In addition, we determined levels of IgG antibodies in the plasma in GBM (n = 82), MMA (n = 83), and controls (non-tumor CNS disorders and healthy donors, n = 50) with capture ELISA. We discovered that GBM plasma EVs are smaller in size and had no relationship between size and concentration. Importantly, GBM EVs purified from both plasma and tumor cell lines produced IgG-mediated, complement-dependent apoptosis and necrosis in primary human neurons, mouse brain slices, and neuroblastoma cells. The unique phenotype of GBM EVs may contribute to its neuronal cytotoxicity, providing insight into its role in tumor pathogenesis.

• Item Type: Articles
• Additional Information: This study was funded by grants from the National Institute of Health NIMH1R21MH118174-01 and 4R33MH118174 and the Department of Neurosurgery Research Funds.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Kennedy, Professor Peter
• Authors: Zhou, W., Lovasz, D., Zizzo, Z., He, Q., Coughlan, C., Kowalski, R. G., Kennedy, P. G.E., Graner, A. N., Lillehei, K. O., Ormond, D. R., Youssef, A. S., Graner, M. W., and Yu, X.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Journal Name: Biomedicines
• Publisher: MDPI
• ISSN: 2227-9059
• ISSN (Online): 2227-9059
• Published Online: 27 October 2022
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First published in Biomedicines 10(11): 2718
• Publisher Policy: Reproduced under a Creative Commons License