N‐cadherin‐mediated adhesion and aberrant catenin expression in anaplastic thyroid‐carcinoma cell lines

The role of cadherins and catenins in the progression of thyroid carcinoma is unclear. We have investigated α‐, β‐ and γ‐catenins and p120 ctn in relation to the expression of cadherins in human anaplastic thyroid‐carcinoma cell lines (HTh7, HTh74, C643 and SW1736) with Western blotting and immunofluorescence. E‐cadherin was lacking except in SW1736, which consisted of E‐cadherin‐positive (approx. 5%) and ‐negative cells. The α‐ and β‐catenin levels were similar to those of primary cultured non‐neoplastic (E‐cadherin‐positive) human thyrocytes. In contrast, the expression of γ‐catenin was low and variable, correlating with the different levels of cytokeratin in the same cells (HTh74 > SW1736 > C643 > HTh7). p120 ctn resolved as a doublet in Western blots; the approximately 100‐kDa band also found in non‐neoplastic epithelial cells was reduced whereas the approximately 115‐kDa band, corresponding to the fibroblast‐type isoform of p120 ctn , was neo‐expressed. A DNA‐demethylating agent, 5‐aza‐2′‐deoxycytidine, up‐regulated E‐cadherin in SW1736 and γ‐catenin in SW1736 and C643, whereas the other cell lines were unresponsive; other catenins were not affected. The catenins were generally distributed along the cell borders. Immunostaining, cell‐surface biotinylation and co‐immunoprecipitation revealed that all cell lines expressed N‐cadherin in connection with β‐catenin at the plasma membrane. Incubation with an N‐cadherin antibody disrupted cell‐cell adhesion. We conclude that E‐cadherin‐negative anaplastic thyroid‐carcinoma cell lines display functional N‐cadherin/β‐catenin complexes, partial or complete loss of γ‐catenin, and isoform shift of p120 ctn . The unequal expression of E‐cadherin and γ‐catenin and the variable response to DNA de‐methylation suggest that anaplastic thyroid carcinoma is not a uniform entity. Int. J. Cancer 83:692–699, 1999. © 1999 Wiley‐Liss, Inc.