CHARACTERIZATION OF HUMAN COLON-CARCINOMA VARIANT CELLS SELECTED FOR SIALYL LE(X) CARBOHYDRATE ANTIGEN - LIVER COLONIZATION AND ADHESION TOVASCULAR ENDOTHELIAL-CELLS

The content df sialyl Lewis-X antigen (Neu5Ac alpha 2-3Gal beta 1-4(Fu c 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 cel l surface sialyl Le(X) were isolated from the heterogeneous KM12C cell s to characterize the biological behavior of colon carcinoma cells wit h elevated cell surface contents of sialyl Le(X). When these cells wer e injected intrasplenically into nude mice, KM12-HX cells colonized to the liver more efficiently than KM12-LX cells, Under in vitro conditi ons, 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 sp ecific for E-selectin, which was known to serve as a ligand for the si alyl Le(X) carbohydrate antigen, The treatment of KM12-HX cells with b enzyl N-acetyl-alpha-D-galactosaminide, a putative inhibitor of the ex tension of O-linked carbohydrate chains, reduced the rate of adhesion, These results suggested that the interaction of endothelial cell surf ace E-selectin with O-linked carbohydrate chains on colon carcinoma ce ll surface glycoproteins played an important role in the adhesion. (C) 1995 Academic Press, Inc.