N-cadherin-mediated adhesion and aberrant catenin expression in anaplasticthyroid-carcinoma cell lines

The role of cadherins and catenins in the progression of thyroid carcinoma is unclear. We have investigated as beta- and gamma-catenins and p120(ctn) in relation to the expression of cadherins in human anaplastic thyroid-carc inoma cell lines (HTh7, HTh74, C643 and SW 1736) with Western blotting and immunofluorescence. E-cadherin was lacking except in SW1736, which consiste d of E-cadherin-positive (approx. 5%) and -negative cells. The alpha- and b eta-catenin levels were similar to those of primary cultured non-neoplastic (E-cadherin-positive) human thyrocytes. In contrast, the expression of gam ma-catenin was low and variable, correlating with the different levels of c ytokeratin in the same cells (HTh74 > SW1736 > C643 > HTh7). p120(ctn) reso lved as a doublet in Western blots; the approximately 100-kDa band also fou nd in nonneoplastic epithelial cells was reduced whereas the approximately 115-kDa band, corresponding to the fibroblast-type isoform of p 120(ctn), w as neo-expressed. A DNA-demethylating agent, 5-aza-2'-deoxycytidine, up-reg ulated E-cadherin in SW1736 and gamma-catenin in SWI736 and C643, whereas t he other cell lines were unresponsive; other catenins were not affected. Th e catenins were generally distributed along the cell borders. Immunostainin g, cell-surface biotinylation and co-immunoprecipitation revealed that all cell lines expressed N-cadherin in connection with beta-catenin at the plas ma membrane, Incubation with an N-cadherin antibody disrupted cell-cell adh esion. We conclude that E-cadherin-negative anaplastic thyroid-carcinoma ce ll lines display functional N-cadherin/beta-catenin complexes, partial or c omplete loss of gamma-catenin, and isoform shift: of p120(ctn). The unequal expression of E-cadherin and gamma-catenin and the variable response to DN A de-methylation suggest that anaplastic thyroid carcinoma is not a uniform entity. (C) 1999 Wiley-liss, Inc.