Degradation of collagen is required for the physiological remodelling of connective tissues during growth and development, as well as in wound healing, inflammatory diseases, and cancer cell invasion. In remodelling adult tissues, degradation of collagen occurs primarily through a phagocytic pathway. While various steps in this pathway have been characterized, the enzyme required to fragment collagen fibrils for phagocytosis has not been identified. Laser confocal microscopy, transmission electron microscopy and biochemical assays were used to show that degradation of collagen substrates by fibroblasts correlated with the expression of the membrane-bound metalloproteinase MT1-MMP (membrane-type 1 matrix metalloproteinase). The MT1-MMP was localized to sites of collagen cleavage on the cell surface and also within the cells. In contrast with MT1-MMP, the gelatinase MMP-2 was not required for collagen phagocytosis. Similar analyses of several ovarian cancer, breast cancer and fibrosarcoma cells indicated that highly metastatic cells also degrade collagen through a phagocytic pathway that is mediated by MT1-MMP. Collectively, these studies demonstrate a pivotal role for catalytically active MT1-MMP in preparing collagen fibrils for phagocytic degradation by normal and transformed cells.
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August 2007
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Conference Article|
July 20 2007
Phagocytosis of collagen by fibroblasts and invasive cancer cells is mediated by MT1-MMP
H. Lee;
H. Lee
*CIHR Group in Matrix Dynamics, Faculty of Dentistry, Room 234, Fitzgerald Building, University of Toronto, 150 College Street, Toronto, ON, Canada M5S 3E2
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K.L. Sodek;
K.L. Sodek
†Department of Cell and Systems Biology, University of Toronto, Toronto, ON, Canada M5S 3G5
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Q. Hwang;
Q. Hwang
*CIHR Group in Matrix Dynamics, Faculty of Dentistry, Room 234, Fitzgerald Building, University of Toronto, 150 College Street, Toronto, ON, Canada M5S 3E2
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T.J. Brown;
T.J. Brown
‡Department of Obstetrics and Gynaecology, University of Toronto, Toronto, ON, Canada, M5G 1L4
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M. Ringuette;
M. Ringuette
†Department of Cell and Systems Biology, University of Toronto, Toronto, ON, Canada M5S 3G5
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J. Sodek
J. Sodek
1
*CIHR Group in Matrix Dynamics, Faculty of Dentistry, Room 234, Fitzgerald Building, University of Toronto, 150 College Street, Toronto, ON, Canada M5S 3E2
1To whom correspondence should be addressed (email jaro.sodek@utoronto.ca)
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Publisher: Portland Press Ltd
Received:
April 16 2007
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2007 Biochemical Society
2007
Biochem Soc Trans (2007) 35 (4): 704–706.
Article history
Received:
April 16 2007
Citation
H. Lee, K.L. Sodek, Q. Hwang, T.J. Brown, M. Ringuette, J. Sodek; Phagocytosis of collagen by fibroblasts and invasive cancer cells is mediated by MT1-MMP. Biochem Soc Trans 1 August 2007; 35 (4): 704–706. doi: https://doi.org/10.1042/BST0350704
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