alpha 1,2Fucosyltransferase increases resistance to apoptosis of rat coloncarcinoma cells

Accumulation of histo-blood group antigens such as Lewis b, Lewis Y and H i n colon cancer is indicative of poor prognosis. It is accompanied by increa se in alpha 1,2fucosyl-transferase activity, a key enzyme for synthesis of these antigens, Using a model of colon carcinoma, we previously showed that alpha 1,2fucosylation increases tumorigenicity, We now show that tumorigen icity inversely correlates with the cells' sensitivity to apoptosis, In add ition, poorly tumorigenic REG cells independently transfected with three di fferent al,2fucosyltransferase cDNAs, the human FUT1, the rat FTA and FTB w ere more resistant than control cells to apoptosis induced in vitro by seru m deprivation, Inversely, PRO cells, spontaneously tumorigenic in immunocom petent syngeneic animals and able to synthesize alpha 1,2fucosylated glycan s, became more sensitive to apoptosis after transfection with a fragment of the FTA cDNA in the antisense orientation. Expression of alpha 1,2fucosylt ransferase in poorly tumorigenic REG cells dramatically enhanced their tumo rigenicity in syngeneic rats. However, in immunodeficient animals, both con trol and al,2fucosyltransferase transfected REG cells were fully tumorigeni c and metastatic, indicating that the presence of al,2fucosylated antigens allowed REG tumor cells to escape immune control. Taken together, the resul ts show that increased tumorigenicity mediated by al,2fucosylation is assoc iated to increased resistance to apoptosis and to escape from immune contro l.