Relationship between alphaGal epitope expression and decrease of tumorigenicity in pancreatic adenocarcinoma model.
The alphaGal epitope is a carbohydrate structure, Galalpha1,3Galbeta1,4GlcNAc-R, synthesized on glycoconjugates in many mammals by alpha1,3galactosyltransferase. Humans do not express this epitope and present in serum large amounts of naturally occuring antibodies, which recognize the alphaGal epitopes and participate in the hyperacute rejection of xenograft. Studies indicated that the fundamental mechanism of hyperacute rejection involving the alphaGal epitope expression can be used in cancer therapy. We have previously suggested that the alphaGal epitope expression by human pancreatic tumoral cells could decrease the tumorigenic behavior of these cells. To determine whether the expression of the alphaGal epitope can modify the tumorigenicity of pancreatic cancer cells, we used a Syrian golden hamster pancreatic adenocarcinoma experimental model. The expression of alphaGal epitopes in the Syrian golden hamster pancreatic cancer cell line HaP-T1 was obtained by selecting stable cell clones transfected with murine alpha1,3galactosyltransferase gene. The alphaGal epitope expression resulted in a delay in the tumoral development of HaP-T1 cells in vivo after allograft transplantation of Syrian golden hamsters (2.5-fold, P < 0.05) and of nude mice. This result is associated with an 100% increase in survival time of nude mice bearing tumors expressing the alphaGal epitope. Our results confirm that the cell surface expression of alphaGal epitope decreases the tumorigenic behavior of pancreatic cancer cells. This novel property may be useful for the development of cancer gene immunotherapy strategy.
Aubert
Muriel
M
INSERM Unité 559, Faculté de Médecine, Université de la Méditerranée EA, 27 boulevard Jean Moulin, 13385 Marseille cedex 5, France.
Crotte
Christian
C
Benkoel
Liliane
L
Panicot-Dubois
Laurence
L
Bernard
Jean-Paul
JP
Lombardo
Dominique
D
Sadoulet
Marie-Odile
MO
Mas
Eric
E
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000818:Animals; D045744:Cell Line, Tumor; D006224:Cricetinae; D004187:Disaccharides / Q000235:genetics*; D004195:Disease Models, Animal; D000939:Epitopes / Q000235:genetics; D005700:Galactosyltransferases / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008647:Mesocricetus; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D010957:Plasmids; D012016:Reference Values; D014162:Transfection
D004187:Disaccharides; D000939:Epitopes; C055075:galactosyl-(1-3)galactose; D005700:Galactosyltransferases