DENSITY-DEPENDENT REGULATION OF CELL-SURFACE ASSOCIATION OF MATRIX METALLOPROTEINASE-2 (MMP-2) IN BREAST-CARCINOMA CELLS

Degradation of extracellular matrix takes place in areas of cell-matri x contacts and is partly carried out by the action of matrix metallopr oteinases (MMP). MMP-2 is a member of the MMP family that has been ass ociated with breast-cancer metastasis. In the present study, we invest igated the association of MMP-2 to the surface of breast-cancer cells and revealed an MMP-2-binding site that is expressed on sparsely plate d cells and which is progressively lost as the cells approach confluen ce. Gelatin zymography, immunostaining and flow cytometry of MDA-MB-23 1 cells from sparse cultures demonstrated binding both of latent and o f activated exogenous MMP-2, while little or no binding of MMP-2 was o bserved in confluent culture. Analysis of the expression of MT1-MMP, T IMP-2 and alpha v integrin, 3 proteins shown to play a role in cell-su rface association of MMP-2, revealed enhanced levels of these proteins in confluent MDA-MB-231 cells. Thus, the reduced MMP-2 binding to con fluent cells is not related to a deficiency in these MMP-2-binding pro teins. Taken together, these studies suggest that MMP-2 binding to the surface of breast-cancer cells is regulated by cell-cell interactions and that tumor cells invading from the main tumor mass can up-regulat e their MMP-2-binding capacity to acquire greater invasive capacity. ( C) 1998 Wiley-Liss, Inc.