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Cancer cells’ ability to mechanically adjust to extracellular matrix stiffness correlates with their invasive potential

Increased tissue stiffness is a classic characteristic of solid tumors. One of the major contributing factors is increased density of collagen fibers in the extracellular matrix (ECM). Here, we investigate how cancer cells biomechanically interact with and respond to the stiffness of the ECM. Probin...

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Autores principales: Wullkopf, Lena, West, Ann-Katrine V., Leijnse, Natascha, Cox, Thomas R., Madsen, Chris D., Oddershede, Lene B., Erler, Janine T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6233061/
https://www.ncbi.nlm.nih.gov/pubmed/30091653
http://dx.doi.org/10.1091/mbc.E18-05-0319
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author Wullkopf, Lena
West, Ann-Katrine V.
Leijnse, Natascha
Cox, Thomas R.
Madsen, Chris D.
Oddershede, Lene B.
Erler, Janine T.
author_facet Wullkopf, Lena
West, Ann-Katrine V.
Leijnse, Natascha
Cox, Thomas R.
Madsen, Chris D.
Oddershede, Lene B.
Erler, Janine T.
author_sort Wullkopf, Lena
collection PubMed
description Increased tissue stiffness is a classic characteristic of solid tumors. One of the major contributing factors is increased density of collagen fibers in the extracellular matrix (ECM). Here, we investigate how cancer cells biomechanically interact with and respond to the stiffness of the ECM. Probing the adaptability of cancer cells to altered ECM stiffness using optical tweezers–based microrheology and deformability cytometry, we find that only malignant cancer cells have the ability to adjust to collagen matrices of different densities. Employing microrheology on the biologically relevant spheroid invasion assay, we can furthermore demonstrate that, even within a cluster of cells of similar origin, there are differences in the intracellular biomechanical properties dependent on the cells’ invasive behavior. We reveal a consistent increase of viscosity in cancer cells leading the invasion into the collagen matrices in comparison with cancer cells following in the stalk or remaining in the center of the spheroid. We hypothesize that this differential viscoelasticity might facilitate spheroid tip invasion through a dense matrix. These findings highlight the importance of the biomechanical interplay between cells and their microenvironment for tumor progression.
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spelling pubmed-62330612018-12-16 Cancer cells’ ability to mechanically adjust to extracellular matrix stiffness correlates with their invasive potential Wullkopf, Lena West, Ann-Katrine V. Leijnse, Natascha Cox, Thomas R. Madsen, Chris D. Oddershede, Lene B. Erler, Janine T. Mol Biol Cell Brief Reports Increased tissue stiffness is a classic characteristic of solid tumors. One of the major contributing factors is increased density of collagen fibers in the extracellular matrix (ECM). Here, we investigate how cancer cells biomechanically interact with and respond to the stiffness of the ECM. Probing the adaptability of cancer cells to altered ECM stiffness using optical tweezers–based microrheology and deformability cytometry, we find that only malignant cancer cells have the ability to adjust to collagen matrices of different densities. Employing microrheology on the biologically relevant spheroid invasion assay, we can furthermore demonstrate that, even within a cluster of cells of similar origin, there are differences in the intracellular biomechanical properties dependent on the cells’ invasive behavior. We reveal a consistent increase of viscosity in cancer cells leading the invasion into the collagen matrices in comparison with cancer cells following in the stalk or remaining in the center of the spheroid. We hypothesize that this differential viscoelasticity might facilitate spheroid tip invasion through a dense matrix. These findings highlight the importance of the biomechanical interplay between cells and their microenvironment for tumor progression. The American Society for Cell Biology 2018-10-01 /pmc/articles/PMC6233061/ /pubmed/30091653 http://dx.doi.org/10.1091/mbc.E18-05-0319 Text en © 2018 Wullkopf et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License.
spellingShingle Brief Reports
Wullkopf, Lena
West, Ann-Katrine V.
Leijnse, Natascha
Cox, Thomas R.
Madsen, Chris D.
Oddershede, Lene B.
Erler, Janine T.
Cancer cells’ ability to mechanically adjust to extracellular matrix stiffness correlates with their invasive potential
title Cancer cells’ ability to mechanically adjust to extracellular matrix stiffness correlates with their invasive potential
title_full Cancer cells’ ability to mechanically adjust to extracellular matrix stiffness correlates with their invasive potential
title_fullStr Cancer cells’ ability to mechanically adjust to extracellular matrix stiffness correlates with their invasive potential
title_full_unstemmed Cancer cells’ ability to mechanically adjust to extracellular matrix stiffness correlates with their invasive potential
title_short Cancer cells’ ability to mechanically adjust to extracellular matrix stiffness correlates with their invasive potential
title_sort cancer cells’ ability to mechanically adjust to extracellular matrix stiffness correlates with their invasive potential
topic Brief Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6233061/
https://www.ncbi.nlm.nih.gov/pubmed/30091653
http://dx.doi.org/10.1091/mbc.E18-05-0319
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