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.