Down-regulation of E-cadherin in mouse skin carcinoma cells enhances a migratory and invasive phenotype linked to matrix metalloproteinase-9 gelatinase expression

Lab Invest. 1998 Sep;78(9):1131-42.


To assess the role of gelatinases in mouse skin tumor progression and their link to the expression of E-cadherin (E-CD), the cell-cell adhesion protein, we used the highly metastatic squamous HaCa4 cell line and several HaCa4-derived clones obtained by transfection of the mouse E-CD cDNA. Expression of matrix metalloproteinase-9 (MMP-9) mRNA and protein activity were present in E-CD (-) HaCa4 and control clones in culture, but they were strongly diminished in E-CD (+) clones (E24 and E62) at subconfluence. To explore the suppressive effect of the cell-cell contacts mediated by E-CD on MMP-9 expression, we introduced a plasmid encoding mouse E-CD antisense cDNA into the E24 cell clone. The transfectant P1-clones obtained with reduced or absent E-CD expression showed increased levels of MMP-9 gelatinase, motility in vitro, and metastatic potential in vivo. Expression of MMP-9 in the various cell clones was also negatively modulated by cell density, but this effect was much stronger in E-CD (+) cells, despite the fact that all of the cell clones analyzed maintained the expression of P-cadherin and made cell-cell contacts at high cell density. Our results indicate that in this cell system, the E-CD-mediated cell-cell contacts are involved in the down-regulation of MMP-9 expression. Thus, the loss of E-CD triggers a migratory and invasive phenotype in mouse squamous carcinoma cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antisense Elements (Genetics) / genetics
  • Antisense Elements (Genetics) / pharmacology
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Cell Count
  • Cell Movement / drug effects
  • Collagenases / genetics
  • Collagenases / metabolism*
  • DNA, Complementary / genetics
  • Epidermis / metabolism
  • Epidermis / pathology
  • Lung Neoplasms / pathology
  • Lung Neoplasms / secondary
  • Male
  • Matrix Metalloproteinase 9
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Invasiveness / physiopathology
  • Phenotype
  • Promoter Regions, Genetic / genetics
  • RNA, Messenger / metabolism
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / pathology
  • Tumor Cells, Cultured


  • Antisense Elements (Genetics)
  • Cadherins
  • DNA, Complementary
  • RNA, Messenger
  • Collagenases
  • Matrix Metalloproteinase 9