H-BLOOD-GROUP ANTIGEN CARRIED BY CD44V MODULATES TUMORIGENICITY OF RAT COLON-CARCINOMA CELLS

Expression of carbohydrate ABH blood group antigens is oncodevelopment ally regulated and their presence on tumor cells constitutes a prognos tic factor. However, it is not clear whether they directly affect tumo r behavior. Using a rat model of colon carcinoma, we previously observ ed an association between the presence of H blood group antigens and t umorigenicity in syngeneic animals. In the present study, we show by i mmunoprecipitation experiments that cell surface H blood group antigen s of a highly tumorigenic clone (PROb) are essentially carried by spli ce variants of the CD44 molecule containing exon V6. PROb cells were t hen transfected with an antisense fragment of the gene coding for a ra t alpha(1-2)fucosyltransferase. This enzyme allows synthesis of H anti gens from various beta-galactoside precursors. Transfected subclones o f PROb cells were obtained which had significantly decreased enzymatic activity and H antigenic: cell surface levels. In contrast, no such c hanges were observed in control cells transfected with either the empt y vector or with a sense fragment of the gene. Compared to controls, t he 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 pr esence of the fucosylated structures on CD44 could modulate the functi ons of this adhesion molecule.