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Review

Physics of Brain Cancer: Multiscale Alterations of Glioblastoma Cells under Extracellular Matrix Stiffening

1
Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands
2
Polymer Science, Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands
3
Department of Biomedical Engineering-FB40, University of Groningen, University Medical Center Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands
4
W.J. Kolff Institute for Biomedical Engineering and Materials Science-FB41, University of Groningen, University Medical Center Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands
*
Authors to whom correspondence should be addressed.
Academic Editors: Inge S. Zuhorn and Enrico Mastrobattista
Pharmaceutics 2022, 14(5), 1031; https://doi.org/10.3390/pharmaceutics14051031
Received: 30 March 2022 / Revised: 27 April 2022 / Accepted: 6 May 2022 / Published: 10 May 2022
(This article belongs to the Collection Drug Delivery in The Netherlands)
The biology and physics underlying glioblastoma is not yet completely understood, resulting in the limited efficacy of current clinical therapy. Recent studies have indicated the importance of mechanical stress on the development and malignancy of cancer. Various types of mechanical stress activate adaptive tumor cell responses that include alterations in the extracellular matrix (ECM) which have an impact on tumor malignancy. In this review, we describe and discuss the current knowledge of the effects of ECM alterations and mechanical stress on GBM aggressiveness. Gradual changes in the brain ECM have been connected to the biological and physical alterations of GBM cells. For example, increased expression of several ECM components such as glycosaminoglycans (GAGs), hyaluronic acid (HA), proteoglycans and fibrous proteins result in stiffening of the brain ECM, which alters inter- and intracellular signaling activity. Several mechanosensing signaling pathways have been identified that orchestrate adaptive responses, such as Hippo/YAP, CD44, and actin skeleton signaling, which remodel the cytoskeleton and affect cellular properties such as cell–cell/ECM interactions, growth, and migration/invasion of GBM cells. In vitro, hydrogels are used as a model to mimic the stiffening of the brain ECM and reconstruct its mechanics, which we also discuss. Overall, we provide an overview of the tumor microenvironmental landscape of GBM with a focus on ECM stiffening and its associated adaptive cellular signaling pathways and their possible therapeutic exploitation. View Full-Text
Keywords: physics of cancer; glioblastoma multiforme; extracellular matrix stiffening; tumor microenvironment; mechanical stress; adaptive cellular signaling physics of cancer; glioblastoma multiforme; extracellular matrix stiffening; tumor microenvironment; mechanical stress; adaptive cellular signaling
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MDPI and ACS Style

Khoonkari, M.; Liang, D.; Kamperman, M.; Kruyt, F.A.E.; van Rijn, P. Physics of Brain Cancer: Multiscale Alterations of Glioblastoma Cells under Extracellular Matrix Stiffening. Pharmaceutics 2022, 14, 1031. https://doi.org/10.3390/pharmaceutics14051031

AMA Style

Khoonkari M, Liang D, Kamperman M, Kruyt FAE, van Rijn P. Physics of Brain Cancer: Multiscale Alterations of Glioblastoma Cells under Extracellular Matrix Stiffening. Pharmaceutics. 2022; 14(5):1031. https://doi.org/10.3390/pharmaceutics14051031

Chicago/Turabian Style

Khoonkari, Mohammad, Dong Liang, Marleen Kamperman, Frank A.E. Kruyt, and Patrick van Rijn. 2022. "Physics of Brain Cancer: Multiscale Alterations of Glioblastoma Cells under Extracellular Matrix Stiffening" Pharmaceutics 14, no. 5: 1031. https://doi.org/10.3390/pharmaceutics14051031

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