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

Farideh Sabeh; Ichiro Ota; Kenn Holmbeck; Henning Birkedal-Hansen; Paul Soloway; Milagros Balbin; Carlos Lopez-Otin; Steven Shapiro; Masaki Inada; Stephen Krane; Edward Allen; Duane Chung; Stephen J Weiss

doi:10.1083/jcb.200408028

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

Farideh Sabeh, Ichiro Ota, Kenn Holmbeck, Henning Birkedal-Hansen, Paul Soloway, Milagros Balbin, Carlos Lopez-Otin, Steven Shapiro, Masaki Inada, Stephen Krane, Edward Allen, Duane Chung, Stephen J Weiss

461 Citationer (Scopus)

Abstract

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.

Originalsprog	Engelsk
Tidsskrift	The Journal of Cell Biology
Vol/bind	167
Udgave nummer	4
Sider (fra-til)	769-81
Antal sider	13
ISSN	0021-9525
DOI	https://doi.org/10.1083/jcb.200408028
Status	Udgivet - 22 nov. 2004

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10.1083/jcb.200408028

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Sabeh, F., Ota, I., Holmbeck, K., Birkedal-Hansen, H., Soloway, P., Balbin, M., Lopez-Otin, C., Shapiro, S., Inada, M., Krane, S., Allen, E., Chung, D., & Weiss, S. J. (2004). Tumor cell traffic through the extracellular matrix is controlled by the membrane-anchored collagenase MT1-MMP. The Journal of Cell Biology, 167(4), 769-81. https://doi.org/10.1083/jcb.200408028

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

abstract = "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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author = "Farideh Sabeh and Ichiro Ota and Kenn Holmbeck and Henning Birkedal-Hansen and Paul Soloway and Milagros Balbin and Carlos Lopez-Otin and Steven Shapiro and Masaki Inada and Stephen Krane and Edward Allen and Duane Chung and Weiss, {Stephen J}",

year = "2004",

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doi = "10.1083/jcb.200408028",

language = "English",

volume = "167",

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T1 - Tumor cell traffic through the extracellular matrix is controlled by the membrane-anchored collagenase MT1-MMP

AU - Sabeh, Farideh

AU - Ota, Ichiro

AU - Holmbeck, Kenn

AU - Birkedal-Hansen, Henning

AU - Soloway, Paul

AU - Balbin, Milagros

AU - Lopez-Otin, Carlos

AU - Shapiro, Steven

AU - Inada, Masaki

AU - Krane, Stephen

AU - Allen, Edward

AU - Chung, Duane

AU - Weiss, Stephen J

PY - 2004/11/22

Y1 - 2004/11/22

N2 - 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.

AB - 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.

KW - Animals

KW - Cell Membrane/metabolism

KW - Cell Movement/genetics

KW - Cells, Cultured

KW - Chick Embryo

KW - Coculture Techniques

KW - Collagen/metabolism

KW - Collagenases/metabolism

KW - Extracellular Matrix/metabolism

KW - Fibroblasts/cytology

KW - Gene Targeting

KW - Matrix Metalloproteinase 13

KW - Matrix Metalloproteinase 14

KW - Matrix Metalloproteinase 2/metabolism

KW - Matrix Metalloproteinase 3/metabolism

KW - Matrix Metalloproteinase 9/metabolism

KW - Matrix Metalloproteinases, Membrane-Associated

KW - Metalloendopeptidases/genetics

KW - Mice

KW - Mice, Knockout

KW - Neoplasm Invasiveness

KW - Neoplasms/enzymology

KW - Phenotype

U2 - 10.1083/jcb.200408028

DO - 10.1083/jcb.200408028

M3 - Journal article

C2 - 15557125

SN - 0021-9525

VL - 167

SP - 769

EP - 781

JO - Journal of Cell Biology

JF - Journal of Cell Biology

IS - 4

ER -

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

Abstract

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