Abstract
Structural changes in the extracellular matrix are necessary for cell migration during tissue remodeling and tumor invasion. Specific cleavage of laminin-5 (Ln-5) by matrix metalloprotease-2 (MMP2) was shown to induce migration of breast epithelial cells. MMP2 cleaved the Ln-5 gamma2 subunit at residue 587, exposing a putative cryptic promigratory site on Ln-5 that triggers cell motility. This altered form of Ln-5 is found in tumors and in tissues undergoing remodeling, but not in quiescent tissues. Cleavage of Ln-5 by MMP2 and the resulting activation of the Ln-5 cryptic site may provide new targets for modulation of tumor cell invasion and tissue remodeling.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Breast / cytology*
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Breast / metabolism
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Cell Adhesion
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Cell Adhesion Molecules / metabolism*
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Cell Division
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Cell Line
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Cell Movement*
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Cell Size
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Collagenases / metabolism
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Epithelial Cells
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Epithelium / metabolism
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Extracellular Matrix / metabolism*
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Female
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Fibrinolysin / metabolism
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Gelatinases / antagonists & inhibitors
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Gelatinases / metabolism*
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Humans
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Kalinin
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Matrix Metalloproteinase 2
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Matrix Metalloproteinase 9
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Metalloendopeptidases / antagonists & inhibitors
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Metalloendopeptidases / metabolism*
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Mice
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Phenylalanine / analogs & derivatives
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Phenylalanine / pharmacology
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Protease Inhibitors / pharmacology
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Rats
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Recombinant Fusion Proteins / metabolism
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Skin Neoplasms / metabolism
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Skin Neoplasms / pathology
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Thiophenes / pharmacology
Substances
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Cell Adhesion Molecules
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Protease Inhibitors
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Recombinant Fusion Proteins
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Thiophenes
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Phenylalanine
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batimastat
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Fibrinolysin
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Collagenases
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Gelatinases
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Metalloendopeptidases
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Matrix Metalloproteinase 2
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Matrix Metalloproteinase 9