Cell-cell adhesion molecules and their associated proteins in bladder cancer cells and their role in mitogen induced cell-cell dissociation and invasion.
Three bladder cell lines (EJ138, RT112/84 and T24/83) were used to examine the expression of E-cadherin, desmoglein, their associated proteins and their role in cell-cell dissociation and invasion using hepatocyte growth factor/scatter factor (HGF/SF). Both immunocytochemistry and Western blotting revealed that RT112/84 cells expressed high levels of E-cadherin, alpha-, beta-, and gamma-catenins. However, there was no expression of E-cadherin and very low levels of alpha- and beta-catenin expression detected in both EJ138 and T24/83 cells. In contrast, all three cell lines were found to express desmoglein, desmoplakin and c-Met. An in vitro invasion assay showed that both EJ138 and T24/83 cells were highly invasive, however, RT112/84 cells were found to have very limited invasion. Invasion of RT112/84 cells was significantly increased by inclusion of either antibody to E-cadherin or motogen (HGF/SF) in the culture medium. This did not appear to be the case for EJ138 and T24/83 cells. Using immunoprecipitation, HGF/SF induced tyrosine phosphorylation of beta-catenin but not desmoplakin. It is concluded that E-cadherin plays a stronger role than desmosomal cadherin in the control of the in vitro invasion of bladder cancer cells. Activation of beta-catenin and subsequent dysfunction of E-cadherin may be a key mechanism in the induction of invasion by the motogen, HGF/SF.
Davies
G
G
University Department of Surgery, University of Wales College of Medicine, Heath Park, Cardiff, U.K. DAVIESG11@cf.ac.uk
Jiang
W G
WG
Mason
M D
MD
D000818:Animals; D015820:Cadherins / Q000032:analysis*; D003598:Cytoskeletal Proteins / Q000032:analysis* / Q000378:metabolism; D051182:Desmogleins; D051180:Desmoplakins; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D019859:Proto-Oncogene Proteins c-met / Q000032:analysis; D015534:Trans-Activators; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000737:chemistry / Q000473:pathology*; D051176:beta Catenin
C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D015820:Cadherins; D003598:Cytoskeletal Proteins; C495294:DSP protein, human; D051182:Desmogleins; D051180:Desmoplakins; C495295:Dsp protein, mouse; D015534:Trans-Activators; D051176:beta Catenin; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met