Biomedical subjects

Christian Crotte

Publications and source records attributed to Christian Crotte.

3 recordsLinked to original sources

PubMed2005

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.

Adenocarcinoma↗

PubMed2003

Decrease of human pancreatic cancer cell tumorigenicity by alpha1,3galactosyltransferase gene transfer.

The enzyme alpha1,3galactosyltransferase synthesizes the alphaGal epitope, a carbohydrate structure (Galalpha1,3Galbeta1,4GlcNAc-R), on glycoconjugates in lower mammals. The enzyme is absent in humans but large amounts of natural antibodies that recognize alphaGal epitopes are present in human serum. It is likely that these antibodies contribute to the host defense and participate in the hyperacute rejection of xenograft. Previous studies indicated that the glycosyltransferase gene transfer into tumoral cells can modify the structure of glycoconjugates at the cell surface and, as a consequence, modulates the metastatic and tumorigenic behaviors of these cells. The aim of our study was to determine whether the expression of alphaGal epitope can modify the tumorigenicity of human pancreatic cancer cells. The expression of alphaGal epitopes in the human pancreatic cancer cell lines BxPC-3 and Panc-1 was obtained by selecting stable cell clones transfected with murine alpha1,3galactosyltransferase gene. The expression of the enzyme activity in BxPC-3 and Panc-1 cells resulted in the formation at the cell surface of alphaGal epitopes that are recognized by human anti-alphaGal antibodies. alphaGal epitope expression at the surface of pancreatic cancer cells was associated with the fixation of complement 1q to human anti-alphaGal antibodies. The alphaGal epitope expression also resulted in a delay in the tumoral development of BxPC-3 and Panc-1 cells in vivo after xenograft transplantation of nude mice. In addition to the impairment of the metastatic potential of murine tumor cell lines and the activation of immune response, our study provides evidence that the cell surface expression of alphaGal epitopes also modulates the tumorigenic behavior of human pancreatic cancer cells.

Animals↗

PubMedDate not supplied

Monoclonal antibody 16D10 to the C-terminal domain of the feto-acinar pancreatic protein binds to membrane of human pancreatic tumoral SOJ-6 cells and inhibits the growth of tumor xenografts.

Feto-acinar pancreatic protein (FAPP) characterized by mAbJ28 reactivity is a specific component associated with ontogenesis and behaves as an oncodevelopment-associated antigen. We attempted to determine whether pancreatic tumoral SOJ-6 cells are expressed at their surface FAPP antigens and to examine if specific antibodies directed against these FAPP epitopes could decrease the growth of pancreatic tumors in a mice model. For this purpose, we used specific antibodies against either the whole FAPP, the O-glycosylated C-terminal domain, or the N-terminal domain of the protein. Our results indicate that SOJ-6 cells expressed at their surface a 32-kDa peptide corresponding to the C-terminal domain of the FAPP. Furthermore, we show, by using endoproteinase Lys-C or geldanamycin, a drug able to impair the FAPP secretion, that this 32-kDa peptide expressed on the SOJ-6 cell surface comes from the degradation of the FAPP. Finally, an in vivo prospective study using a preventative tumor model in nude mice indicates that targeting this peptide by the use of mAb16D10 inhibits the growth of SOJ-6 xenografts. The specificity of mAb16D10 for pancreatic tumors and the possibility to obtain recombinant structures of mucin-like peptides recognized by mAb16D10 and mAbJ28 are promising tools in immunologic approaches to cure pancreatic cancers.

Animals↗