Increase of rat colon carcinoma cells tumorigenicity by α(l–2) fucosyltransferase gene transfection

Abstract

Fucosylated histo-blood group antigens such as Lewis b, Lewis Y, and H accumulate in colon carcinoma and this is accompanied by a clear increase in α(1–2)fucosyltransfer-ase activity, a key enzyme for the biosynthesis of these antigens. Yet the biological significance of α(1–2)fucosylated structures is not well defined. We have trans-fected a poorly tumorigenic rat colon carcinoma cell line with the human H blood group α(1–2)fucosyltransferase cDNA. This resulted in cell surface expression of H antigens with a concomitant decrease of sialic acid substituted and free β-galactosides. Immunoprecipitation experiments showed that H antigens were essentially borne by variants of CD44 carrying amino acid sequences encoded by exon v6. The transfected cells showed increased motility in a wound healing assay, without changing their proliferation rates. Parental and control cells transfected with an empty vector formed small tumors that always regressed after 30 days when injected subcutaneously to syngeneic rats. In contrast, α(1–2)fucosyltransferase transfectants were able to form progressive tumors. Increased tumorigenicity was also visible in nude mice. These results demonstrate that α(1–2)fucosylated antigens contribute directly to aggressiveness of colon carcinoma cells. This could occur by altering a function of CD44 variants.