Characterization of N-cadherin-containing cell-cell contacts of the liver

Cell-cell contacts play a pivotal role for multicellular organisms, not only in development, but also in tumour formation and progression, and molecular components of cell-cell contact structures are used with increasing frequency in immunohistochemical tumour diagnosis. Notably, cadherins, transmembrane glycoproteins of adherens junctions, are discussed to be involved in cancer formation and metastasis. In hepatocarcinogenesis, some reports have claimed that loss of E-cadherin, the classical epithelial cadherin, would promote tumour spread, and – surprisingly – others have also reported positive immunoreactions for N-cadherin in hepatic tumour cells. As N-cadherin had not been described in hepatocytes before, our intention was to characterize the localization and composition of N-cadherin-containing adherens junctions in human and animal liver. With immunofluorescence and -electron microscopy as well as proteinbiochemical methods, including immunoprecipitation, we examined the possible relationship between E- and N-cadherin-containing junctions in normal and fetal liver as well as in cultured cells derived therefrom. In normal liver, N-cadherin-containing adherens junctions can be found near bile canaliculi and at the basolateral membrane–here partly together with E-cadherin. Using PLC („Alexander“) cells, a line derived from primary liver carcinoma, an intrinsic heterogeneity could be noted with cells containing both E- and N-cadherin, besides cells containing N- or E-cadherin, in both situations colocalizing with α- and β-catenin, plakoglobin, protein p120 ctn and vinculin. Future experiments will have to elucidate the molecular relationship and the assembly processes in the diverse junctions of the liver, in liver development and regeneration, and the possible functions of this dual cadherin system, with respect to tumour formation.