Microenvironmental stiffness induces metabolic reprogramming in glioblastoma

Alireza Sohrabi; Austin E.Y.T. Lefebvre; Mollie J. Harrison; Michael C. Condro; Talia M. Sanazzaro; Gevick Safarians; Itay Solomon; Soniya Bastola; Shadi Kordbacheh; Nadia Toh; Harley I. Kornblum; Michelle A. Digman; Stephanie K. Seidlits

Cell Reports (Oct 2023)

Microenvironmental stiffness induces metabolic reprogramming in glioblastoma

Alireza Sohrabi,
Austin E.Y.T. Lefebvre,
Mollie J. Harrison,
Michael C. Condro,
Talia M. Sanazzaro,
Gevick Safarians,
Itay Solomon,
Soniya Bastola,
Shadi Kordbacheh,
Nadia Toh,
Harley I. Kornblum,
Michelle A. Digman,
Stephanie K. Seidlits

Affiliations

Alireza Sohrabi: Department of Biomedical Engineering, University of Texas at Austin, Austin, TX 78712, USA; Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA
Austin E.Y.T. Lefebvre: Department of Biomedical Engineering, University of California at Irvine, Irvine, CA 92697, USA
Mollie J. Harrison: Department of Biomedical Engineering, University of Texas at Austin, Austin, TX 78712, USA
Michael C. Condro: Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
Talia M. Sanazzaro: Department of Biomedical Engineering, University of Texas at Austin, Austin, TX 78712, USA
Gevick Safarians: Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA
Itay Solomon: Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA
Soniya Bastola: Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
Shadi Kordbacheh: Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA
Nadia Toh: Department of Biomedical Engineering, University of Texas at Austin, Austin, TX 78712, USA
Harley I. Kornblum: Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
Michelle A. Digman: Department of Biomedical Engineering, University of California at Irvine, Irvine, CA 92697, USA
Stephanie K. Seidlits: Department of Biomedical Engineering, University of Texas at Austin, Austin, TX 78712, USA; Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA; Corresponding author

Journal volume & issue: Vol. 42, no. 10
p. 113175

Abstract

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Summary: The mechanical properties of solid tumors influence tumor cell phenotype and the ability to invade surrounding tissues. Using bioengineered scaffolds to provide a matrix microenvironment for patient-derived glioblastoma (GBM) spheroids, this study demonstrates that a soft, brain-like matrix induces GBM cells to shift to a glycolysis-weighted metabolic state, which supports invasive behavior. We first show that orthotopic murine GBM tumors are stiffer than peritumoral brain tissues, but tumor stiffness is heterogeneous where tumor edges are softer than the tumor core. We then developed 3D scaffolds with μ-compressive moduli resembling either stiffer tumor core or softer peritumoral brain tissue. We demonstrate that the softer matrix microenvironment induces a shift in GBM cell metabolism toward glycolysis, which manifests in lower proliferation rate and increased migration activities. Finally, we show that these mechanical cues are transduced from the matrix via CD44 and integrin receptors to induce metabolic and phenotypic changes in cancer cells.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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