Differential Effects of Extracellular Vesicles from Two Different Glioblastomas on Normal Human Brain Cells.

Autor: Wang M; Department of Neurosurgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Graner AN; Department of Neurosurgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Knowles B; Department of Neurosurgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USA., McRae C; Department of Neurosurgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.; Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35233, USA., Fringuello A; Department of Neurosurgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.; Department of Cell Biology, State University of New York Downstate Health Sciences University, New York, NY 11203, USA., Paucek P; Department of Neurosurgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Gavrilovic M; Department of Neurosurgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.; Department of Biomedical Sciences, Regis University, Denver, CO 80221, USA.; St Louis University School of Medicine, St. Louis, MO 63104, USA., Redwine M; Department of Neurosurgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.; Department of Biomedical Sciences, Regis University, Denver, CO 80221, USA., Hanson C; Department of Neurosurgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.; Department of Biomedical Sciences, Regis University, Denver, CO 80221, USA., Coughlan C; Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Grimaldo-Garcia S; Department of Neurosurgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.; Department of Neuroscience, Middlebury College, Middlebury, VT 05753, USA., Metzger B; Department of Neurosurgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.; Occupational Therapy, Illinois College, Jacksonville, IL 62650, USA.; Neuroscience, Midwestern University, Glendale, AZ 85308, USA., Bolus V; Department of Neurosurgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.; Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35233, USA., Kopper TJ; Department of Neurosurgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Smith M; Department of Neurosurgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Zhou W; Department of Neurosurgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Lenz M; Department of Neurosurgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.; Occupational Therapy, Illinois College, Jacksonville, IL 62650, USA., Abosch A; Department of Neurosurgery, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA., Ojemann S; Department of Neurosurgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Lillehei KO; Department of Neurosurgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Yu X; Department of Neurosurgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA., Graner MW; Department of Neurosurgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Jazyk: angličtina
Zdroj: Neurology international [Neurol Int] 2024 Nov 06; Vol. 16 (6), pp. 1355-1384. Date of Electronic Publication: 2024 Nov 06.
DOI: 10.3390/neurolint16060103
Abstrakt: Background/Objectives: Glioblastomas (GBMs) are dreadful brain tumors with abysmal survival outcomes. GBM extracellular vesicles (EVs) dramatically affect normal brain cells (largely astrocytes) constituting the tumor microenvironment (TME). We asked if EVs from different GBM patient-derived spheroid lines would differentially alter recipient brain cell phenotypes. This turned out to be the case, with the net outcome of treatment with GBM EVs nonetheless converging on increased tumorigenicity. Methods: GBM spheroids and brain slices were derived from neurosurgical patient tissues following informed consent. Astrocytes were commercially obtained. EVs were isolated from conditioned culture media by ultrafiltration, concentration, and ultracentrifugation. EVs were characterized by nanoparticle tracking analysis, electron microscopy, biochemical markers, and proteomics. Astrocytes/brain tissues were treated with GBM EVs before downstream analyses. Results: EVs from different GBMs induced brain cells to alter secretomes with pro-inflammatory or TME-modifying (proteolytic) effects. Astrocyte responses ranged from anti-viral gene/protein expression and cytokine release to altered extracellular signal-regulated protein kinase (ERK1/2) signaling pathways, and conditioned media from EV-treated cells increased GBM cell proliferation. Conclusions: Astrocytes/brain slices treated with different GBM EVs underwent non-identical changes in various omics readouts and other assays, indicating "personalized" tumor-specific GBM EV effects on the TME. This raises concern regarding reliance on "model" systems as a sole basis for translational direction. Nonetheless, net downstream impacts from differential cellular and TME effects still led to increased tumorigenic capacities for the different GBMs.
Databáze: MEDLINE