Expression of sialyl 6-sulfo Lewis X is inversely correlated with conventional sialyl Lewis X expression in human colorectal cancer

Sialyl 6-sulfo Lewis X determinant has been described recently as a major l igand for L-selectin on high endothelial venules of human peripheral lymph nodes. From our investigation of its distribution in human colorectal cance r tissues and cultured colon cancer cells, the sialyl 6-sulfo Lewis X deter minant was preferentially expressed in the nonmalignant colonic epithelia r ather than cancer cells (P < 0.001; n = 23), This was in contrast to the di stribution of conventional sialyl Lewis X, which was preferentially express ed in cancer tissues rather than nonmalignant epithelia (P = 0.007; n = 23) , indicating that 6-sulfation predominantly occurs in nonmalignant tissues and is suppressed upon malignant transformation. In confirmation of this, a nonsialylated determinant 6-sulfo Lewis X was also found to be preferentia lly localized in the nonmalignant epithelia, Significant expression of sial yl 6-sulfo Lewis X was observed in only 2 lines, whereas 8 were positive fo r conventional sialyl Lewis X, among 13 cultured colon cancer cell lines. T ransfection of cells with fucosyltransferase (Fuc-T) VI induced expression of sialyl 6-sulfo Lewis X, whereas transfection of Fuc-T III did not, sugge sting that the determinant was synthesized mainly by Fuc-T VI in colonic ep ithelia, Members of the sialic acid cyclase pathway, the de-N-acetyl sialyl 6-sulfo Lewis X and cyclic sialyl 6-sulfo Lewis X determinants, were also preferentially expressed in the nonmalignant epithelia rather than colonic cancer cells (P < 0.001; n = 23). Stimulation of the sialyl 6-sulfo Lewis X -positive colon cancer cell line with a calcium ionophore ionomycin markedl y reduced sialyl 6-sulfo Lewis X and induced cyclic sialyl 6-sulfo Lewis X expression. These results suggested that the metabolic conversion of sialyl 6-sulfo Lewis X into cyclic sialyl 6-sulfo Lewis X by a calcium-dependent enzyme, sialic acid cyclase, as we hypothesized for human leukocytes previo usly (C, Mitsuoka et at, Proc. Natl, Acad, Sci, USA, 96: 1597-1602, 1999), also occurs in nonmalignant colonic epithelia.