Density-dependent regulation of cell-surface association of matrix metalloproteinase-2 (MMP-2) in breast-carcinoma cells

Int J Cancer. 1998 Jan 19;75(2):259-65. doi: 10.1002/(sici)1097-0215(19980119)75:2<259::aid-ijc15>;2-8.


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 MTI-MMP, TIMP-2 and alpha(v) 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.

MeSH terms

  • Antigens, CD / analysis
  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / pathology
  • Cell Count
  • Female
  • Flow Cytometry
  • Gelatinases / metabolism*
  • Humans
  • Immunohistochemistry
  • Integrin alphaV
  • Matrix Metalloproteinase 2
  • Metalloendopeptidases / metabolism*
  • Tissue Inhibitor of Metalloproteinase-2 / pharmacology
  • Tumor Cells, Cultured


  • Antigens, CD
  • Integrin alphaV
  • Tissue Inhibitor of Metalloproteinase-2
  • Gelatinases
  • Metalloendopeptidases
  • Matrix Metalloproteinase 2