Phenotype and Neuronal Cytotoxic Function of Glioblastoma Extracellular Vesicles

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 characteri...

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Bibliographic Details
Published in:Biomedicines 2022-10, Vol.10 (11), p.2718
Main Authors: Zhou, Wenbo, Lovasz, Daniel, Zizzo, Zoë, He, Qianbin, Coughlan, Christina, Kowalski, Robert G, Kennedy, Peter G E, Graner, Arin N, Lillehei, Kevin O, Ormond, D Ryan, Youssef, A Samy, Graner, Michael W, Yu, Xiaoli
Format: Article
Language:English
Subjects:
Alzheimer's disease
Apoptosis
Biomarkers
Brain cancer
Brain research
Brain slice preparation
Brain tumors
Cancer therapies
Cell interactions
Cytotoxicity
Electron microscopy
Extracellular vesicles
Glioblastoma
Glioblastoma multiforme
Health aspects
IgG
Immunoglobulin G
Immunotherapy
Meningioma
Microscopy
Nanoparticles
Neuroblastoma
Neuroblasts
Neurons
Neurosurgery
Pathogenesis
Phenotypes
Plasma
Proteins
Proteomics
Radiation therapy
Tumor cell lines
Tumor cells
Tumor microenvironment
Tumors
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Summary: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.
ISSN:2227-9059
2227-9059
DOI:10.3390/biomedicines10112718