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Soft matrix is a natural stimulator for cellular invasiveness

Directional mesenchymal cell invasion in vivo is understood to be a stimulated event and to be regulated by cytokines, chemokines, and types of extracellular matrix (ECM). Instead, by focusing on the cellular response to ECM stiffness, we found that soft ECM (low stiffness) itself is sufficient to p...

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Autores principales: Gu, Zhizhan, Liu, Fei, Tonkova, Elina A., Lee, Soo Young, Tschumperlin, Daniel J., Brenner, Michael B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3923638/
https://www.ncbi.nlm.nih.gov/pubmed/24336521
http://dx.doi.org/10.1091/mbc.E13-05-0260
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author Gu, Zhizhan
Liu, Fei
Tonkova, Elina A.
Lee, Soo Young
Tschumperlin, Daniel J.
Brenner, Michael B.
author_facet Gu, Zhizhan
Liu, Fei
Tonkova, Elina A.
Lee, Soo Young
Tschumperlin, Daniel J.
Brenner, Michael B.
author_sort Gu, Zhizhan
collection PubMed
description Directional mesenchymal cell invasion in vivo is understood to be a stimulated event and to be regulated by cytokines, chemokines, and types of extracellular matrix (ECM). Instead, by focusing on the cellular response to ECM stiffness, we found that soft ECM (low stiffness) itself is sufficient to prevent stable cell-to-cell adherens junction formation, up-regulate matrix metalloproteinase (MMP) secretion, promote MMP activity, and induce invadosome-like protrusion (ILP) formation. Consistently, similar ILP formation was also detected in a three-dimensional directional invasion assay in soft matrix. Primary human fibroblasts spontaneously form ILPs in a very narrow range of ECM stiffness (0.1–0.4 kPa), and such ILP formation is Src family kinase dependent. In contrast, spontaneous ILP formation in malignant cancer cells and fibrosarcoma cells occurs across a much wider range of ECM stiffness, and these tumor cell ILPs are also more prominent at lower stiffness. These findings suggest that ECM softness is a natural stimulator for cellular invasiveness.
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spelling pubmed-39236382014-04-30 Soft matrix is a natural stimulator for cellular invasiveness Gu, Zhizhan Liu, Fei Tonkova, Elina A. Lee, Soo Young Tschumperlin, Daniel J. Brenner, Michael B. Mol Biol Cell Articles Directional mesenchymal cell invasion in vivo is understood to be a stimulated event and to be regulated by cytokines, chemokines, and types of extracellular matrix (ECM). Instead, by focusing on the cellular response to ECM stiffness, we found that soft ECM (low stiffness) itself is sufficient to prevent stable cell-to-cell adherens junction formation, up-regulate matrix metalloproteinase (MMP) secretion, promote MMP activity, and induce invadosome-like protrusion (ILP) formation. Consistently, similar ILP formation was also detected in a three-dimensional directional invasion assay in soft matrix. Primary human fibroblasts spontaneously form ILPs in a very narrow range of ECM stiffness (0.1–0.4 kPa), and such ILP formation is Src family kinase dependent. In contrast, spontaneous ILP formation in malignant cancer cells and fibrosarcoma cells occurs across a much wider range of ECM stiffness, and these tumor cell ILPs are also more prominent at lower stiffness. These findings suggest that ECM softness is a natural stimulator for cellular invasiveness. The American Society for Cell Biology 2014-02-15 /pmc/articles/PMC3923638/ /pubmed/24336521 http://dx.doi.org/10.1091/mbc.E13-05-0260 Text en © 2014 Gu et al. 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 (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Gu, Zhizhan
Liu, Fei
Tonkova, Elina A.
Lee, Soo Young
Tschumperlin, Daniel J.
Brenner, Michael B.
Soft matrix is a natural stimulator for cellular invasiveness
title Soft matrix is a natural stimulator for cellular invasiveness
title_full Soft matrix is a natural stimulator for cellular invasiveness
title_fullStr Soft matrix is a natural stimulator for cellular invasiveness
title_full_unstemmed Soft matrix is a natural stimulator for cellular invasiveness
title_short Soft matrix is a natural stimulator for cellular invasiveness
title_sort soft matrix is a natural stimulator for cellular invasiveness
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3923638/
https://www.ncbi.nlm.nih.gov/pubmed/24336521
http://dx.doi.org/10.1091/mbc.E13-05-0260
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