Article

E-Cadherin mediates MMP down-regulation in highly invasive bronchial tumor cells.

Institut National de la Santé et de la Recherche Mèdicale (INSERM) Unité Mixte de Recherche Santé (UMRS) 514, Laboratoire Pol Bouin, Reims, France.
American Journal Of Pathology (impact factor: 4.89). 09/2003; 163(2):653-61. DOI:10.1016/S0002-9440(10)63692-9 pp.653-61
Source: PubMed

ABSTRACT The disorganization of E-cadherin/catenin complexes and the overexpression of matrix metalloproteinases (MMPs) are frequently involved in the capacity of epithelial cells to acquire an invasive phenotype. The functional link between E-cadherin and MMPs was studied by transfecting invasive bronchial BZR tumor cells with human E-cadherin cDNA. Using different in vitro (cell dispersion, modified Boyden chamber) and in vivo assays (human airway epithelial xenograft), we showed that E-cadherin-positive clones displayed a decrease of invasive abilities. As shown by immunoprecipitation, the re-expressed E-cadherin was able to sequestrate one part of free cytoplasmic beta-catenin in BZR cells. The decrease of beta-catenin transcriptional activity in E-cadherin-transfected clones was demonstrated using the TOP-FLASH reporter construct. Finally, we observed a decrease of MMP-1, MMP-3, MMP-9, and MT1-MMP, both at the mRNA and at the protein levels, in E-cadherin-positive clones whereas no changes in MMP-2, TIMP-1, or TIMP-2 were observed when compared with control clones. Moreover, zymography analysis revealed a loss of MMP-2 activation ability in E-cadherin-positive clones treated with the concanavalin A lectin. These data demonstrate a direct role of E-cadherin/catenin complex organization in the regulation of MMPs and suggest an implication of this regulation in the expression of an invasive phenotype by bronchial tumor cells.

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Keywords

Boyden chamber
 
bronchial tumor cells
 
BZR cells
 
cell dispersion
 
E-cadherin-positive clones
 
E-cadherin-transfected clones
 
E-cadherin/catenin complex organization
 
E-cadherin/catenin complexes
 
epithelial cells
 
free cytoplasmic beta-catenin
 
functional link
 
human E-cadherin cDNA
 
invasive abilities
 
invasive phenotype
 
MMP-2 activation ability
 
protein levels
 
re-expressed E-cadherin
 
transfecting invasive bronchial BZR tumor cells
 
vivo assays
 
zymography analysis