Characterization of Human Colon Carcinoma Variant Cells Selected for Sialyl Lex Carbohydrate Antigen: Liver Colonization and Adhesion to Vascular Endothelial Cells

Abstract The content of sialyl Lewis-X antigen (Neu5Acα2-3Galβ1-4(Fucα1-3)GlcNAc-R: sialyl Le x ) was previously shown to correlate with the progression of human colon carcinomas to the advanced stages. Variant cell lines with high (KM12-HX) or low (KM12-LX) levels of cell surface sialyl Le x were isolated from the heterogeneous KM12C cells to characterize the biological behavior of colon carcinoma cells with elevated cell surface contents of sialyl Le x . When these cells were injected intrasplenically into nude mice, KM12-HX cells colonized to the liver more efficiently than KM12-LX cells. Under in vitro conditions, KM12-HX cells demonstrated greater degree of adhesion to cytokine-activated human umbilical vein endothelial cells than KM12-LX cells. The adhesion of KM12-HX cells was partially inhibited by antibodies specific for E-selectin, which was known to serve as a ligand for the sialyl Le x carbohydrate antigen. The treatment of KM12-HX cells with benzyl N -acetyl-α-D-galactosaminide, a putative inhibitor of the extension of O-linked carbohydrate chains, reduced the rate of adhesion. These results suggested that the interaction of endothelial cell surface E-selectin with O-linked carbohydrate chains on colon carcinoma cell surface glycoproteins played an important role in the adhesion.