CYTOPLASMIC REDISTRIBUTION OF E-CADHERIN-CATENIN ADHESION COMPLEX IS ASSOCIATED WITH DOWN-REGULATED TYROSINE PHOSPHORYLATION OF E-CADHERIN IN HUMAN BRONCHOPULMONARY CARCINOMAS

The E-cadherin-catenin complex, by mediating intercellular adhesion, r egulates the architectural integrity of epithelia. Down-regulation of its expression is thought to contribute to invasion of carcinoma cells . To investigate the involvement of the E-cadherin-catenin adhesion sy stem in the progression of human bronchopulmonary carcinomas, we compa red the immunohistochemical distribution of E-cadherin, alpha-catenin, and beta-catenin in four human bronchial cancer cell Lines with diffe rent invasive abilities and in 44 primary bronchopulmonary tumors. Alt hough invasive bronchial cell lines did not express E-cadherin and a-c atenin, complete down-regulation of cadherin-catenin complex expressio n was a rare event in vivo in bronchopulmonary carcinomas. Nevertheles s, a spotty and cytoplasmic pattern of E-cadherin and catenins was obs erved in 32 primary tumors, only in invasive tumor clusters. Immunopre cipitation experiments showed that this redistribution was not related to a disruption of cadherin-catenin interaction but to down-regulated tyrosine phosphorylation of E-cadherin, We conclude that loss of E-ca dherin and/or catenins is not a prominent early event in the invasive progression of human bronchopulmonary carcinomas in vivo. The decrease d tyrosine phosphorylation of E-cadherin may reflect a loss of functio nality of the complex and implicates a major role in tumor invasion.