Carbohydrate-mediated cell adhesion as a determinant of colorectal cancer metastasis
HUMAN COLORECTAL carcinomas with increased metastatic potential and poor prognosis are characterized by the high content of sialyl-Lewis X carbohydrate antigen (Neu5Acα2-3Galβ1-4 [Fucα1-3]GlcNAc-R). The levels of these carbohydrate antigens apparently increase during colorectal carcinoma progression from nonmetastatic to metastatic tumors and inversely correlate with postoperative survival of colon carcinoma patients, as revealed by retrospective studies. Cell lines selected for high levels of cell surface sialyl-Lewis X antigen metastasize to livers when they are injected intrasplenically into nude mice. The high expresser cells also strongly adhere to activated endothelial cells apparently through E-selectin. Increased expression of sialyl-Lewis X antigens on the surface of the high expresser variant cells with greater metastatic potentials is apparently due to increased α-3-fucosyltransferase, a biosynthetic enzyme presumably responsible for the final step of the production of sialyl-Lewis X antigens. We propose that the sialyl-Lewis X carbohydrate antigen is one of the unique molecular phenotypes that determine colorectal cancer metastasis.
