Colorectal Cancer Metastasis Determined by Carbohydrate Antigen Sialy Lewis X-Inhibition of Metastatic Phenotypes by the Modification of Carbohydrorate Structure

Abstract

Sialyl Lewis-X antigen (sLe^x) and sialy Lewis-a antigen (sLe^a) are expressed in colorectal carcinomas and were recently shown to be a Iigand for endothelial adhesion molecule E-selectin. In order to determined whether expression of cell surface sLex and sLe^a is associated with the metastatic potential of human colorectal carcinoma (CRC), we examined sLe^x and sLe^a expression in tissue samples obtained from 159 CRC patients to investigate whether this antigen expression could serve as a prognostic parameter, and examined metastatic phenotypes in variant CRC cell lines for high and low cell surface levels of sLe^x (KM12HX and KM12LX, respectively). Clinical records showed that the disease-free survival rate for CRC patients with high levels of sLex was significantly poorer than for patients with low levels of this antigen. Cox's multivariate analysis revealed that the sLex expression level was one of the significant discriminants of recurrence in colorectal cancer patients. KM12HX showed a higher metastatic potential in nude mice and greater adhesive ability in vitro than KM12LX cells. This increased adhesiveness of KM12HX was inhibited by anti-E-selectin antibody, an inhibitor of carbohydrate synthesis, benzyl-N-acetyl-α-D-galactosaminide, and sialidase. These results suggest that sLe^x expression could be involved in colon cancer metastasis and that sLe^x might prove to be a potent marker of recurrence in CRC patients. Also, they suggest the possibility of regulation of the metastatic potential of CRC by inhibition of carbohydrate antigen synthesis.