Z Gastroenterol 2011; 49 - P2_86
DOI: 10.1055/s-0030-1269603

E-/ N-cadherin cis-heterodimer-bearing puncta adhaerentia as a hallmark for epithelia and derived tumors of the hepatopancreaticobiliary system

BK Straub 1, J Boda-Heggemann 2, UF Pape 2, R Zimbelmann 2, S Rickelt 2, C Grund 2, C Kuhn 2, S Singer 3, P Schirmacher 3, WW Franke 2
  • 1Pathologisches Institut der Universität Heidelberg, Heidelberg, Heidelberg
  • 2Helmholtz-Professur Zellbiologie, Deutsches Krebsforschungszentrum, Heidelberg
  • 3Pathologisches Institut, Universitätsklinikum Heidelberg, Heidelberg

Cell-cell junctions play a pivotal role in cell development and in cell functions, but also in tumor formation and progression. Cadherins, transmembrane glycoproteins of adherens junctions (AJs), such as the epithelial E-cadherin and the neural/ mesenchymal N-cadherin, are widely believed to act in a homophilic, tissue-specific manner and are attributed mutually exclusive roles in development, as well as in carcinogenesis and metastasis. Hitherto only E-cadherin has been described in AJ of normal hepatocytes. Yet, in previous work we could show that large amounts of both E- and N-cadherin are found in the same puncta adhaerentia junctions of hepatocytes and other endoderm-derived epithelial cell types.

With (immuno)-electron microscopy, confocal laser scanning microscopy as well as proteinbiochemical methods including immunoprecipitation and chemical cross-linking, we could show, that a large portion of E- and N-cadherin in normal hepatocytes exists as cis-E: N-cadherin heterodimers in a near isostoichometric ratio. E- and N-cadherin complexes could also be identified in embryonal and fetal liver, starting at least at day 11 of mouse development. In hepatocellular tumors, E- and N-cadherin were coexpressed in hepatocellular adenomas, hepatoblastomas, and in the vast majority of hepatocellular carcinomas. Besides, colocalization of E- and N-cadherin was noted in related endoderm-derived tissues such as bile and pancreas ducts as well as in cholangiocarcinomas and in lesser amount in ductal adenocarcinomas of the pancreas. In some hepatocellular carcinomas and cholangiocarcinomas as well as in cells of the lines PLC, HepG2, HuH7 and Hep3B, partial segregation of E- and N-cadherin-dimers was noted with puncta positive for either E- or N-cadherin or both.

In summary, cis-E: N-cadherin-heterodimer-based AJ constitute a novel AJ type characteristic of normal and malignantly transformed hepatocytes and related intercepts of endoderm-derived epithelia and tumors.

E-cadherin - N-cadherin - adherens junctions - hepatocellular carcinoma - hepatocytes