Control of sialyl Lewis X antigen expression in the colon by fucosyltransferase VI and beta4 GalNAcT-II

Sialyl Lewis X (sLex) is a well known carbohydrate antigen whose overexpression in cancer correlates with metastasis. In colon cancer, the molecular bases of sLex overexpression remain elusive. We have investigated sLex expression in normal and cancer colonic tissues and in cell lines as a function of the expression of fucosyltransferases and beta4GalNAcT-II. This enzyme, which is downregulated in colon cancers, is responsible for the biosynthesis of the Sda antigen [Siaalpha2,3(GalNAcbeta1,4)Galbeta1,4GlcNAc], whose biosynthesis competes with that of sLex. In colon cancers and cell lines, sLex expression correlates with a fucosyltransferase activity able to fucosylate 3'sialyllactosamine at low (0.5 mM) concentration. Transfection experiments with FucT-III, IV, V, VI and VII cDNAs in COS-7 cells indicate that only FucT-VI displays this property. In gastrointestinal cell lines, high levels of this fucosyltransferase activity are shown by cell lines expressing high levels of the FucT-VI transcript. In normal colon, sLex antigen is detectable upon de-acetylation but its expression does not correlate with any fucosyltransferase activity or transcript. Rather, we observed a significant correlation between sLex and the ratio between fucosyltransferase activity with 0.5 mM 3'sialyllactosamine and beta4GalNAcT-II activity. These data suggest that in both normal and cancer colonic tissues the biosynthesis of sLex is mainly due to FucT-VI or to a fucosyltransferase with similar kinetic properties, unknown at present. In normal colon, but not in colon cancers, the fucosyltransferase activity above described is counteracted by competing glycosyltransferases, as the high beta4GalNAcT-II activity that synthesizes the alternative Sda antigen.