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, 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 (K(D) of approximately 2.5 nM) and capacity (approximately 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.
Berton
A
A
Cell Biology Unit, Christian de Duve Institute of Cellular Pathology and Université catholique de Louvain, UCL-ICP 7541, Avenue Hippocrate 75, 1200, Brussels, Belgium.
Selvais
C
C
Lemoine
P
P
Henriet
P
P
Courtoy
P J
PJ
Marbaix
E
E
Emonard
H
H
D002384:Catalysis; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004717:Endometrium / Q000502:physiology; D004847:Epithelial Cells / Q000502:physiology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism
D011498:Protein Precursors; D019716:Tissue Inhibitor of Metalloproteinase-2; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7