Binding of matrilysin-1 to human epithelial cells promotes its activity

Matrix metalloproteinase-7 (MMP-7, matrilysin- 1) modulates crucial biological events by processing many epithelial cell surface-associated effectors. We addressed MMP-7 interaction with human epithelial cells and its resulting activity. In human endometrium, a model of controlled tissue remodeling,...

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Bibliographic Details
Published in:Cellular and molecular life sciences : CMLS 2007-03, Vol.64 (5), p.610-620
Main Authors: Berton, A, Selvais, C, Lemoine, P, Henriet, P, Courtoy, P. J, Marbaix, E, Emonard, H
Format: Article
Language:English
Subjects:
Catalysis
Cell Line
Cell Membrane - metabolism
cell surface
Cells
Cells, Cultured
Cellular biology
Endometrium - physiology
Epithelial Cells - physiology
epithelium
Female
Heparan sulfate
Humans
Immunohistochemistry
Matrix Metalloproteinase 7 - metabolism
MMP-7
Protein Precursors - metabolism
proteolytic activity
resistance to inhibition
Tissue Inhibitor of Metalloproteinase-2 - metabolism
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Summary:Matrix metalloproteinase-7 (MMP-7, matrilysin- 1) modulates crucial biological events by processing many epithelial cell surface-associated effectors. We addressed MMP-7 interaction with human epithelial cells and its resulting activity. In human endometrium, a model of controlled tissue remodeling, proMMP-7 was diffusely immunolocalized inside epithelial cells, whereas MMP-7 delineated their entire plasma membrane. Endometrial explants preferentially retained active MMP-7, but not proMMP-7. Endometrial epithelial cells and carcinoma cells from various tissues bound active MMP-7. Endometrial carcinoma-derived Ishikawa cells showed high affinity (KD of ~2.5 nM) and capacity (~260 000 sites per cell) for MMP-7. MMP-7 binding decreased by extracting membrane sterols or interfering with heparan sulfate proteoglycans, and was abrogated by tissue inhibitors of metalloproteinase-2 (TIMP-2) or synthetic MMP inhibitors. Bound MMP-7 not only remained fully active towards a macromolecular substrate but also became resistant to TIMP-2. We conclude that MMP-7-selective targeting to the plasma membrane of epithelial cells promotes its activity by conferring resistance to TIMP-2.
ISSN:1420-682X
1420-9071
DOI:10.1007/s00018-007-6415-5