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

Shoji Nakamori, Masao Kameyama, Shingi Imaoka, Takushi Yasuda, Hiroshi Nakano, Hiroaki Ohigashi, Masahiro Hiratsuka, Yo Sasaki, Osamu Ishikawa, Toshiyuki Kabuto, Hiroshi Furukawa, Takeshi Iwanaga, Yuki Izumi*, Tatsuro Irimura*

Department of Surgery, The Center for Adult Diseases, Osaka
*Department of Chemical Toxicology and Immunochemistry, Faculty of Pharmacoseutical Science, The University of Tokyo

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 ligand for endothelial adhesion molecule E-selectin. In order to determined whether expression of cell surface sLe^x 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 (KMl2HX and KM12LX, respectively). Clinical records showed that the disease-free survival rate for CRC patients with high levels of sLe^x was significantly poorer than for patients with low levels of this antigen. Cox's multivariate analysis revealed that the sLe^x 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 KMl2HX 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.

Key words
colorectam cancer, metastasis, carbohydrate, antigen

Reprint requests
Shoji Nakamori Department of Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases
1-3-3 Nakamichi, Higashinari, Osaka, 537 JAPAN

Accepted
November 15, 1995

To read the PDF file you will need Abobe Reader installed on your computer.