H Blood Group Antigen Carried by CD44V Modulates Tumorigenicity of Rat Colon Carcinoma Cells

Expression of carbohydrate ABH blood group antigens Is oncodevelopmentally regulated and their presence on tumor ceHs constitutes a prognostic factor. However, It is not clear whether they directly affect tumor behavior. Using a rat model of colon carcinoma, we previously observed an association between the presence of H blood group antigens and tumorigealcity in syngeneic animals. In the present study, we show by immunoprecipltation experiments that cell surface H blood group antigens of a highly tumorigenic clone (PROb) are essentially carried by splice variants of the CD44 molecule containing exon V6. PROb cells were then transfected with an antisense fragment of the gene coding for a rat α(l–2)fucosyltransferase. This enzyme allows synthesis of H antigens from various β-galactoside precursors. Transfected subcloaes of PROb cells were obtained which had significantly decreased enzymatic activity and H antigenic cell surface levels. In contrast, no such changes were observed in control cells transfected with either the empty vector or with a sense fragment of the gene. Compared to controls, the antisense-transfected cells were far less tumorigenic in syngeneic animals. These results show that H blood group antigens at the surface of PROb colon carcinoma cells contribute to tumor progression. The presence of the fucosylated structures on CD44 could modulate the functions of this adhesion molecule.