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 greater detail this endothelial binding, we analysed the mRNA expression and function of the enzymes participating in the generation of sLex and sLea on cancer cells. These oligosaccharides are synthesized by sequential action of alpha 2,3 sialyl (alpha 2,3-ST) and alpha 1,3/1,4 fucosyltransferases (alpha 1,3/1,4-FT) on existing (poly)N-acetyllactosamine 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 were observed in adenocarcinoma cell lysates to exogenous N-acetyllactosamine 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 inflammatory 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 cell-surface sLex and sLea. These cells also express mRNA as well as inducible enzyme activities of several alpha 2,3-STs and alpha 1,3/1,4-FTs 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.