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Cells activated for wound repair have the potential to direct collective invasion of an epithelium

Mechanisms regulating how groups of cells are signaled to move collectively from their original site and invade surrounding matrix are poorly understood. Here we develop a clinically relevant ex vivo injury invasion model to determine whether cells involved in directing wound healing have invasive f...

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Detalles Bibliográficos
Autores principales: Bleaken, Brigid M., Menko, A. Sue, Walker, Janice L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4751597/
https://www.ncbi.nlm.nih.gov/pubmed/26658613
http://dx.doi.org/10.1091/mbc.E15-09-0615
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author Bleaken, Brigid M.
Menko, A. Sue
Walker, Janice L.
author_facet Bleaken, Brigid M.
Menko, A. Sue
Walker, Janice L.
author_sort Bleaken, Brigid M.
collection PubMed
description Mechanisms regulating how groups of cells are signaled to move collectively from their original site and invade surrounding matrix are poorly understood. Here we develop a clinically relevant ex vivo injury invasion model to determine whether cells involved in directing wound healing have invasive function and whether they can act as leader cells to direct movement of a wounded epithelium through a three-dimensional (3D) extracellular matrix (ECM) environment. Similar to cancer invasion, we found that the injured cells invade into the ECM as cords, involving heterotypical cell–cell interactions. Mesenchymal cells with properties of activated repair cells that typically locate to a wound edge are present in leader positions at the front of ZO-1–rich invading cords of cells, where they extend vimentin intermediate filament–enriched protrusions into the 3D ECM. Injury-induced invasion depends on both vimentin cytoskeletal function and MMP-2/9 matrix remodeling, because inhibiting either of these suppressed invasion. Potential push and pull forces at the tips of the invading cords were revealed by time-lapse imaging, which showed cells actively extending and retracting protrusions into the ECM. This 3D injury invasion model can be used to investigate mechanisms of leader cell–directed invasion and understand how mechanisms of wound healing are hijacked to cause disease.
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spelling pubmed-47515972016-04-16 Cells activated for wound repair have the potential to direct collective invasion of an epithelium Bleaken, Brigid M. Menko, A. Sue Walker, Janice L. Mol Biol Cell Articles Mechanisms regulating how groups of cells are signaled to move collectively from their original site and invade surrounding matrix are poorly understood. Here we develop a clinically relevant ex vivo injury invasion model to determine whether cells involved in directing wound healing have invasive function and whether they can act as leader cells to direct movement of a wounded epithelium through a three-dimensional (3D) extracellular matrix (ECM) environment. Similar to cancer invasion, we found that the injured cells invade into the ECM as cords, involving heterotypical cell–cell interactions. Mesenchymal cells with properties of activated repair cells that typically locate to a wound edge are present in leader positions at the front of ZO-1–rich invading cords of cells, where they extend vimentin intermediate filament–enriched protrusions into the 3D ECM. Injury-induced invasion depends on both vimentin cytoskeletal function and MMP-2/9 matrix remodeling, because inhibiting either of these suppressed invasion. Potential push and pull forces at the tips of the invading cords were revealed by time-lapse imaging, which showed cells actively extending and retracting protrusions into the ECM. This 3D injury invasion model can be used to investigate mechanisms of leader cell–directed invasion and understand how mechanisms of wound healing are hijacked to cause disease. The American Society for Cell Biology 2016-02-01 /pmc/articles/PMC4751597/ /pubmed/26658613 http://dx.doi.org/10.1091/mbc.E15-09-0615 Text en © 2016 Bleaken 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 for Cell Biology.
spellingShingle Articles
Bleaken, Brigid M.
Menko, A. Sue
Walker, Janice L.
Cells activated for wound repair have the potential to direct collective invasion of an epithelium
title Cells activated for wound repair have the potential to direct collective invasion of an epithelium
title_full Cells activated for wound repair have the potential to direct collective invasion of an epithelium
title_fullStr Cells activated for wound repair have the potential to direct collective invasion of an epithelium
title_full_unstemmed Cells activated for wound repair have the potential to direct collective invasion of an epithelium
title_short Cells activated for wound repair have the potential to direct collective invasion of an epithelium
title_sort cells activated for wound repair have the potential to direct collective invasion of an epithelium
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4751597/
https://www.ncbi.nlm.nih.gov/pubmed/26658613
http://dx.doi.org/10.1091/mbc.E15-09-0615
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