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 ligand for L-selectin on high endothelial venules of human peripheral lymph nodes. From our investigation of its distribution in human colorectal cancer tissues and cultured colon cancer cells, the sialyl 6-sulfo Lewis X determinant was preferentially expressed in the nonmalignant colonic epithelia rather than cancer cells (P < 0.001; n = 23). This was in contrast to the distribution of conventional sialyl Lewis X, which was preferentially expressed 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 preferentially localized in the nonmalignant epithelia. Significant expression of sialyl 6-sulfo Lewis X was observed in only 2 lines, whereas 8 were positive for conventional sialyl Lewis X, among 13 cultured colon cancer cell lines. Transfection of cells with fucosyltransferase (Fuc-T) VI induced expression of sialyl 6-sulfo Lewis X, whereas transfection of Fuc-T III did not, suggesting that the determinant was synthesized mainly by Fuc-T VI in colonic epithelia. 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 markedly 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 previously (C. Mitsuoka et al., Proc. Natl. Acad. Sci. USA, 96: 1597-1602, 1999), also occurs in nonmalignant colonic epithelia.
Izawa
M
M
Program of Experimental Pathology, Aichi Cancer Center, Nagoya, Japan.
Kumamoto
K
K
Mitsuoka
C
C
Kanamori
C
C
Kanamori
A
A
Ohmori
K
K
Ishida
H
H
Nakamura
S
S
Kurata-Miura
K
K
Sasaki
K
K
Nishi
T
T
Kannagi
R
R
D015179:Colorectal Neoplasms / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D016256:Lewis X Antigen / Q000096:biosynthesis*; D008024:Ligands; D009844:Oligosaccharides / Q000096:biosynthesis*; D000080506:Sialyl Lewis X Antigen / Q000031:analogs & derivatives
C086949:6'-sulfated sialyl Lewis x; D016256:Lewis X Antigen; D008024:Ligands; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen