Aberrant E-cadherin and γ-catenin expression in malignant mesothelioma and its diagnostic and biological relevance

Abstract

Cadherins and their associated cytoplasmic proteins, catenins, are critical to the maintenance of normal tissue integrity and the suppression of cancer invasion. The cadherin profile in malignant mesothelioma (MM) is not well defined and the role of the cadherin–catenin system in the pathogenesis of MM remains to be determined. By means of Western blot analysis and immunohistochemistry the expression of E (epithelial)-, N (neural)-, P (placental)-cadherin, and α-, β- and γ-catenins was studied in nine human MM cell lines and five human mesothelial cell lines. Mesothelial cells consistently expressed only N-cadherin and α- and β-catenins. All but one MM cell line were N-cadherin-positive and all of them were also positive for α- and β-catenins. E-cadherin was found in six (66.7%) and γ-catenin in seven (77.8%) MM cell lines. Five of these E-cadherin-positive lines co-expressed N-cadherin and the remaining one was also P-cadherin-positive. Double immunofluorescence staining revealed the plasma membrane co-localisation of both cadherin types in MM cell lines that co-expressed E- and N-cadherin or E- and P-cadherin, respectively. Immunoprecipitation showed complexes of β-catenin with both cadherin types when co-expressed. The results point to upregulation of E-cadherin and γ-catenin in most MM cases and demonstrate that cadherin expression is more heterogeneous and less mutually exclusive in MM compared with the mesothelium, although the biological significance of this finding remains unclear.