alpha1,2Fucosyltransferase increases resistance to apoptosis of rat colon carcinoma cells.
Accumulation of histo-blood group antigens such as Lewis b, Lewis Y and H in colon cancer is indicative of poor prognosis. It is accompanied by increase in alpha1,2fucosyl-transferase activity, a key enzyme for synthesis of these antigens. Using a model of colon carcinoma, we previously showed that alpha1,2fucosylation increases tumorigenicity. We now show that tumorigenicity inversely correlates with the cells' sensitivity to apoptosis. In addition, poorly tumorigenic REG cells independently transfected with three different alpha1,2fucosyltransferase cDNAs, the human FUT1, the rat FTA and FTB were more resistant than control cells to apoptosis induced in vitro by serum deprivation. Inversely, PRO cells, spontaneously tumorigenic in immunocompetent syngeneic animals and able to synthesize alpha1,2fucosylated glycans, became more sensitive to apoptosis after transfection with a fragment of the FTA cDNA in the antisense orientation. Expression of alpha1,2fucosyl-transferase in poorly tumorigenic REG cells dramatically enhanced their tumorigenicity in syngeneic rats. However, in immunodeficient animals, both control and alpha1,2fuco-syltransferase transfected REG cells were fully tumorigenic and metastatic, indicating that the presence of alpha1,2fucosylated antigens allowed REG tumor cells to escape immune control. Taken together, the results show that increased tumorigenicity mediated by alpha1,2fucosyl-ation is associated to increased resistance to apoptosis and to escape from immune control.
Goupille
C
C
INSERM U419, Institut de Biologie, 9 Quai Moncousu, 44035, Nantes, Cedex, France.
Marionneau
S
S
Bureau
V
V
Hallouin
F
F
Meichenin
M
M
Rocher
J
J
Le Pendu
J
J
D000818:Animals; D000942:Antigens, Bacterial / Q000032:analysis; D017209:Apoptosis; D003110:Colonic Neoplasms / Q000201:enzymology / Q000276:immunology / Q000473:pathology*; D018076:DNA, Complementary / Q000235:genetics; D005643:Fucose / Q000378:metabolism; D005647:Fucosyltransferases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D051381:Rats; D014162:Transfection; D014407:Tumor Cells, Cultured; D000097631:Galactoside 2-alpha-L-fucosyltransferase
D000942:Antigens, Bacterial; D018076:DNA, Complementary; D005643:Fucose; D005647:Fucosyltransferases; D000097631:Galactoside 2-alpha-L-fucosyltransferase; C022863:H antigen