EXPRESSION AND FUNCTION OF ALPHA-2,3-SIALYL-TRANSFERASES AND ALPHA-1,3 1,4-FUCOSYL-TRANSFERASES IN COLON ADENOCARCINOMA CELL-LINES - ROLE IN SYNTHESIS OF E-SELECTIN COUNTER-RECEPTORS/

We show here that colon-carcinoma cell lines adhere to E-selectin via sialyl Lewis x and sialyl Lewis a (sLex and sLea) oligosaccharides and that this adhesion can be enhanced by TNF stimulation. To study in gr eater detail this endothelial binding, we analysed the mRNA expression and function of the enzymes participating in the generation of sLex a nd sLea on cancer cells. These oligosaccharides are synthesized by seq uential action of alpha 2,3 sialyl (alpha 2,3-ST) and alpha 1,3/1,4 fu cosyltransferases (alpha 1,3/1,4-FT) on existing (poly)N-acetyllactosa mine chains. We report here that mRNAs of 2 recently cloned alpha 2,3- STs and 4 (alpha 1,3/1,4-FTs are expressed in adenocarcinoma cells. In functional assays alpha 2,3-ST and (alpha 2,3- or 1,4-FT activities w ere observed in adenocarcinoma cell lysates to exogenous N-acetyllacto samine and lacto-N-biose accepters and to their sialylated derivatives , leading to the synthesis of the sialyl-N-acetyllactosamine and sLex or the sialyllacto-N-biose and sLea, respectively. Furthermore, the in flammatory cytokine TNF could enhance some alpha 2,3-ST and alpha 1,3/ 1,4-FT activities capable of generating E-selectin counter-receptors. Taken together, these data show that COLO 205 and HT-29 adenocarcinoma cell lines adhere to E-selectin in a TNF-inducible manner via their c ell-surface sLex and sLea. These cells also express mRNA as well as in ducible enzyme activities of several alpha 2,3-STs and alpha 1,3/1,4-F Ts responsible for the final steps in the synthesis of sLex and sLea. We show here that the TNF-induced adhesion to E-selectin might be due to the increased synthesis of sLex and sLea in colon-carcinoma cells. (C) 1995 Wiley-Liss, Inc.