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Tumor cell traffic through the extracellular matrix is controlled by the membrane-anchored collagenase MT1-MMP

As cancer cells traverse collagen-rich extracellular matrix (ECM) barriers and intravasate, they adopt a fibroblast-like phenotype and engage undefined proteolytic cascades that mediate invasive activity. Herein, we find that fibroblasts and cancer cells express an indistinguishable pericellular col...

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Autores principales: Sabeh, Farideh, Ota, Ichiro, Holmbeck, Kenn, Birkedal-Hansen, Henning, Soloway, Paul, Balbin, Milagros, Lopez-Otin, Carlos, Shapiro, Steven, Inada, Masaki, Krane, Stephen, Allen, Edward, Chung, Duane, Weiss, Stephen J.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172570/
https://www.ncbi.nlm.nih.gov/pubmed/15557125
http://dx.doi.org/10.1083/jcb.200408028
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author Sabeh, Farideh
Ota, Ichiro
Holmbeck, Kenn
Birkedal-Hansen, Henning
Soloway, Paul
Balbin, Milagros
Lopez-Otin, Carlos
Shapiro, Steven
Inada, Masaki
Krane, Stephen
Allen, Edward
Chung, Duane
Weiss, Stephen J.
author_facet Sabeh, Farideh
Ota, Ichiro
Holmbeck, Kenn
Birkedal-Hansen, Henning
Soloway, Paul
Balbin, Milagros
Lopez-Otin, Carlos
Shapiro, Steven
Inada, Masaki
Krane, Stephen
Allen, Edward
Chung, Duane
Weiss, Stephen J.
author_sort Sabeh, Farideh
collection PubMed
description As cancer cells traverse collagen-rich extracellular matrix (ECM) barriers and intravasate, they adopt a fibroblast-like phenotype and engage undefined proteolytic cascades that mediate invasive activity. Herein, we find that fibroblasts and cancer cells express an indistinguishable pericellular collagenolytic activity that allows them to traverse the ECM. Using fibroblasts isolated from gene-targeted mice, a matrix metalloproteinase (MMP)–dependent activity is identified that drives invasion independently of plasminogen, the gelatinase A/TIMP-2 axis, gelatinase B, collagenase-3, collagenase-2, or stromelysin-1. In contrast, deleting or suppressing expression of the membrane-tethered MMP, MT1-MMP, in fibroblasts or tumor cells results in a loss of collagenolytic and invasive activity in vitro or in vivo. Thus, MT1-MMP serves as the major cell-associated proteinase necessary to confer normal or neoplastic cells with invasive activity.
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spelling pubmed-21725702008-03-05 Tumor cell traffic through the extracellular matrix is controlled by the membrane-anchored collagenase MT1-MMP Sabeh, Farideh Ota, Ichiro Holmbeck, Kenn Birkedal-Hansen, Henning Soloway, Paul Balbin, Milagros Lopez-Otin, Carlos Shapiro, Steven Inada, Masaki Krane, Stephen Allen, Edward Chung, Duane Weiss, Stephen J. J Cell Biol Research Articles As cancer cells traverse collagen-rich extracellular matrix (ECM) barriers and intravasate, they adopt a fibroblast-like phenotype and engage undefined proteolytic cascades that mediate invasive activity. Herein, we find that fibroblasts and cancer cells express an indistinguishable pericellular collagenolytic activity that allows them to traverse the ECM. Using fibroblasts isolated from gene-targeted mice, a matrix metalloproteinase (MMP)–dependent activity is identified that drives invasion independently of plasminogen, the gelatinase A/TIMP-2 axis, gelatinase B, collagenase-3, collagenase-2, or stromelysin-1. In contrast, deleting or suppressing expression of the membrane-tethered MMP, MT1-MMP, in fibroblasts or tumor cells results in a loss of collagenolytic and invasive activity in vitro or in vivo. Thus, MT1-MMP serves as the major cell-associated proteinase necessary to confer normal or neoplastic cells with invasive activity. The Rockefeller University Press 2004-11-22 /pmc/articles/PMC2172570/ /pubmed/15557125 http://dx.doi.org/10.1083/jcb.200408028 Text en Copyright © 2004, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Sabeh, Farideh
Ota, Ichiro
Holmbeck, Kenn
Birkedal-Hansen, Henning
Soloway, Paul
Balbin, Milagros
Lopez-Otin, Carlos
Shapiro, Steven
Inada, Masaki
Krane, Stephen
Allen, Edward
Chung, Duane
Weiss, Stephen J.
Tumor cell traffic through the extracellular matrix is controlled by the membrane-anchored collagenase MT1-MMP
title Tumor cell traffic through the extracellular matrix is controlled by the membrane-anchored collagenase MT1-MMP
title_full Tumor cell traffic through the extracellular matrix is controlled by the membrane-anchored collagenase MT1-MMP
title_fullStr Tumor cell traffic through the extracellular matrix is controlled by the membrane-anchored collagenase MT1-MMP
title_full_unstemmed Tumor cell traffic through the extracellular matrix is controlled by the membrane-anchored collagenase MT1-MMP
title_short Tumor cell traffic through the extracellular matrix is controlled by the membrane-anchored collagenase MT1-MMP
title_sort tumor cell traffic through the extracellular matrix is controlled by the membrane-anchored collagenase mt1-mmp
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172570/
https://www.ncbi.nlm.nih.gov/pubmed/15557125
http://dx.doi.org/10.1083/jcb.200408028
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