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A Specific Sequence of the Noncollagenous Domain of the 3(IV) Chain of Type IV Collagen Inhibits Expression and Activation of Matrix Metalloproteinases by Tumor Cells¹

Lab. Biochemistry, IFR 53 Biomolecules, CNRS UPRESA 6021, UFR Medicine, F51095 Reims Cedex, France [S. P., P. G., G. B., F-X. M., J. C. M.]; Department of Medicine and Connective Tissue Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104 [J. H., N. A. K.]; and 75008 Paris, France [J. P. B.]

The invasive properties of melanoma cells correlate with the expression of matrix metalloproteinases (MMPs) and their physiological modulators (tissue inhibitors of metalloproteinase and membrane-type MMPs) and with that of the Vß3 integrin. We investigated the effect of anterior lens capsule type IV collagen and of the 3(IV) collagen chain on the invasive properties of various tumor cell lines (HT-144 melanoma cells, HT-1080 fibrosarcoma cells). We demonstrated that anterior lens capsule type IV collagen or specifically the synthetic peptide 3(IV) 185–203 inhibited both the migration of melanoma or fibrosarcoma cells as well as the activation of membrane-bound MMP-2 by decreasing the expressions of MT1-MMP and the ß3 integrin subunit.

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