Expression of histo-blood group A antigen increases resistance to apoptosis and facilitates escape from immune control of rat colon carcinoma cells.
A and B histo-blood group antigens are present on carcinoma cells at the early stages of cancerogenesis and tend to disappear at later stages, but it is not yet clear whether they take part to the process of tumor progression. To gain some insight into this issue, we used a rat colon carcinoma experimental model. To obtain expression of the A antigen, REG cells were cotransfected with the rat A enzyme cDNA and a rat alpha1,2fucosyltransferase cDNA, either FTA or FTB, whereas PRO cells that spontaneously have alpha1,2fucosyltransferase activity were only transfected with the A enzyme cDNA. All A antigen-expressing transfected cells derived from either REG FTA, REG FTB, or PRO parental cells were more resistant to apoptosis induced by either serum deprivation or heat shock than were their respective controls. When injected to syngeneic immunocompetent rats, A enzyme-transfected PRO cells formed tumors that grew faster than those formed by mock-transfected PRO cells. However, in immunodeficient SCID mice, no difference in growth could be observed between the two types of tumors, indicating that the faster tumor growth of the A antigen-positive cells in immunocompetent animals was due to their higher ability to escape immune control and that this was associated with their higher degree of resistance to apoptosis. These results might explain the slightly augmented incidence of carcinomas observed in A and B blood group individuals compared to O individuals.
Marionneau
Séverine
S
INSERM U419, Institut de Biologie, 9 Quai Moncousu, 44093 Nantes, France.
Le Moullac-Vaidye
Béatrice
B
Le Pendu
Jacques
J
D000017:ABO Blood-Group System / Q000276:immunology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D003110:Colonic Neoplasms / Q000276:immunology* / Q000473:pathology*; D018076:DNA, Complementary / Q000235:genetics; D005647:Fucosyltransferases / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D051379:Mice; D016513:Mice, SCID; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D000097631:Galactoside 2-alpha-L-fucosyltransferase
D000017:ABO Blood-Group System; D018076:DNA, Complementary; D005647:Fucosyltransferases; D011994:Recombinant Proteins; D000097631:Galactoside 2-alpha-L-fucosyltransferase