Characterization of human colon carcinoma variant cells selected for sialyl Lex carbohydrate antigen: liver colonization and adhesion to vascular endothelial cells.

The content of sialyl Lewis-X antigen (Neu5Ac alpha 2-3Gal beta 1-4(fuc alpha 1-3)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-alpha-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.