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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2004
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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. |
format | Text |
id | pubmed-2172570 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2004 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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