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.
Panicot-Dubois
Laurence
L
Institut National de la Santé et de la Recherche Médicale Unité 559 and EA 3289, Faculté de Médecine-Timone, Université de la Méditerranée, Marseilles, France.
Aubert
Muriel
M
Franceschi
Cécile
C
Mas
Eric
E
Silvy
Françoise
F
Crotte
Christian
C
Bernard
Jean-Paul
JP
Lombardo
Dominique
D
Sadoulet
Marie-Odile
MO
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000951:Antigens, Neoplasm / Q000378:metabolism*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D006801:Humans; D008049:Lipase / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000378:metabolism*; D014162:Transfection; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; C054621:CEL protein, human; D008049:Lipase
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