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Density‐dependent regulation of cell‐surface association of matrix metalloproteinase‐2 (MMP‐2) in breast‐carcinoma cells
Author(s) -
Menashi Suzanne,
Dehem Marie,
Souliac Isabelle,
Legrand Yves,
Fridman Rafael
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19980119)75:2<259::aid-ijc15>3.0.co;2-8
Subject(s) - matrix metalloproteinase , breast carcinoma , metalloproteinase , matrix metalloproteinase 9 , association (psychology) , cancer research , carcinoma , matrix (chemical analysis) , breast cancer , medicine , biology , pathology , oncology , chemistry , cancer , psychology , chromatography , psychotherapist
Degradation of extracellular matrix takes place in areas of cell‐matrix contacts and is partly carried out by the action of matrix metalloproteinases (MMP). MMP‐2 is a member of the MMP family that has been associated with breast‐cancer metastasis. In the present study, we investigated the association of MMP‐2 to the surface of breast‐cancer cells and revealed an MMP‐2‐binding site that is expressed on sparsely plated cells and which is progressively lost as the cells approach confluence. Gelatin zymography, immunostaining and flow cytometry of MDA‐MB‐231 cells from sparse cultures demonstrated binding both of latent and of activated exogenous MMP‐2, while little or no binding of MMP‐2 was observed in confluent culture. Analysis of the expression of MT1‐MMP, TIMP‐2 and αv integrin, 3 proteins shown to play a role in cell‐surface association of MMP‐2, revealed enhanced levels of these proteins in confluent MDA‐MB‐231 cells. Thus, the reduced MMP‐2 binding to confluent cells is not related to a deficiency in these MMP‐2‐binding proteins. 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‐regulate their MMP‐2‐binding capacity to acquire greater invasive capacity. Int. J. Cancer 75:259–265, 1998. © 1998 Wiley‐Liss, Inc.