title: 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.
abstract: 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.
authors.affiliation: 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.
authors.forename: Laurence
authors.initials: L
authors.lastname: Panicot-Dubois
authors.forename: Muriel
authors.initials: M
authors.lastname: Aubert
authors.forename: Cécile
authors.initials: C
authors.lastname: Franceschi
authors.forename: Eric
authors.initials: E
authors.lastname: Mas
authors.forename: Françoise
authors.initials: F
authors.lastname: Silvy
authors.forename: Christian
authors.initials: C
authors.lastname: Crotte
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Bernard
authors.forename: Dominique
authors.initials: D
authors.lastname: Lombardo
authors.forename: Marie-Odile
authors.initials: MO
authors.lastname: Sadoulet
mesh_terms: 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
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; C054621:CEL protein, human; D008049:Lipase
references.citation: Am J Surg. 1999 Mar;177(3):257-65
references.pmid: 10219866
references.citation: Ann Oncol. 1999;10 Suppl 4:46-50
references.pmid: 10436784
references.citation: Glycobiology. 1999 Sep;9(9):935-46
references.pmid: 10460835
references.citation: Diabetes. 1999 Dec;48(12):2316-23
references.pmid: 10580419
references.citation: Biochem J. 2000 Jan 1;345 Pt 1:121-8
references.pmid: 10600647
references.citation: J Cell Biochem. 2000 Sep 14;79(4):628-47
references.pmid: 10996854
references.citation: Arch Biochem Biophys. 2000 Nov 1;383(1):1-16
references.pmid: 11097171
references.citation: Biochem J. 2000 Dec 15;352 Pt 3:865-74
references.pmid: 11104697
references.citation: J Biol Chem. 2001 Apr 13;276(15):12356-61
references.pmid: 11148205
references.citation: J Biol Chem. 2001 Apr 6;276(14):11049-54
references.pmid: 11148208
references.citation: Biochim Biophys Acta. 2001 Feb 26;1530(2-3):184-98
references.pmid: 11239821
references.citation: Nature. 2001 May 17;411(6835):380-4
references.pmid: 11357146
references.citation: Glycobiology. 2001 Jul;11(7):565-76
references.pmid: 11447136
references.citation: Biochim Biophys Acta. 2001 Aug 29;1533(1):1-28
references.pmid: 11514232
references.citation: J Neurochem. 2001 Sep;78(5):1083-93
references.pmid: 11553682
references.citation: Semin Oncol. 2002 Dec;29(6 Suppl 20):2-8
references.pmid: 12577227
references.citation: Biochim Biophys Acta. 2003 Apr 7;1621(1):92-101
references.pmid: 12667615
references.citation: Mol Cell Proteomics. 2003 Jun;2(6):388-98
references.pmid: 12821722
references.citation: Breast. 2000 Jun;9(3):130-3
references.pmid: 14731835
references.citation: J Cancer Res Clin Oncol. 1992;118(5):377-85
references.pmid: 1583067
references.citation: Scand J Gastroenterol. 1991 Jul;26(7):787-97
references.pmid: 1896821
references.citation: Pancreas. 1991 Jan;6(1):37-45
references.pmid: 1994378
references.citation: Hum Cell. 1990 Mar;3(1):31-6
references.pmid: 2083222
references.citation: Br J Cancer. 1990 Jul;62(1):118-21
references.pmid: 2390470
references.citation: J Biol Chem. 1987 Sep 15;262(26):12863-70
references.pmid: 2442170
references.citation: Cancer Res. 1989 Mar 15;49(6):1415-21
references.pmid: 2466553
references.citation: J Biol Chem. 1989 Dec 25;264(36):21865-71
references.pmid: 2600091
references.citation: Differentiation. 1987;34(3):210-5
references.pmid: 2892750
references.citation: Biochim Biophys Acta. 1988 Aug 12;961(3):299-308
references.pmid: 3401497
references.citation: Proc Natl Acad Sci U S A. 1986 May;83(10):3407-11
references.pmid: 3458189
references.citation: Int J Cancer. 1986 Aug 15;38(2):155-60
references.pmid: 3733256
references.citation: Nature. 1970 Aug 15;227(5259):680-5
references.pmid: 5432063
references.citation: Cancer Res. 1983 Nov;43(11):5489-92
references.pmid: 6193872
references.citation: Anal Biochem. 1981 Apr;112(2):195-203
references.pmid: 6266278
references.citation: Biochim Biophys Acta. 1980 Jan 11;611(1):147-55
references.pmid: 7350913
references.citation: J Neurosci Res. 1994 Mar 1;37(4):489-96
references.pmid: 7517457
references.citation: Pancreas. 1994 Nov;9(6):692-7
references.pmid: 7531332
references.citation: Eur J Biochem. 1995 Oct 1;233(1):209-18
references.pmid: 7588748
references.citation: Anal Biochem. 1995 Jan 1;224(1):382-9
references.pmid: 7710096
references.citation: Biochemistry. 1995 May 16;34(19):6351-8
references.pmid: 7756263
references.citation: J Biol Chem. 1995 Jun 2;270(22):13524-33
references.pmid: 7768954
references.citation: Eur J Cell Biol. 1994 Oct;65(1):132-44
references.pmid: 7889983
references.citation: Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3077-81
references.pmid: 7909157
references.citation: J Biol Chem. 1993 Dec 5;268(34):25755-63
references.pmid: 8245011
references.citation: Biochem J. 1993 Jan 15;289 ( Pt 2):609-15
references.pmid: 8424803
references.citation: Eur J Cell Biol. 1993 Feb;60(1):115-21
references.pmid: 8462590
references.citation: J Biol Chem. 1996 Mar 22;271(12):7196-202
references.pmid: 8636157
references.citation: Trends Biochem Sci. 1996 Jul;21(7):267-71
references.pmid: 8755249
references.citation: Biochem Biophys Res Commun. 1996 Aug 23;225(3):946-51
references.pmid: 8780715
references.citation: Int J Cancer. 1996 Aug 22;69(4):340-9
references.pmid: 8797880
references.citation: Eur J Biochem. 1997 Jan 15;243(1-2):299-305
references.pmid: 9030752
references.citation: Glycobiology. 1997 Feb;7(1):1-13
references.pmid: 9061359
references.citation: J Biol Chem. 1997 Oct 24;272(43):27353-61
references.pmid: 9341186
references.citation: Biochem J. 1997 Oct 15;327 ( Pt 2):527-35
references.pmid: 9359426
references.citation: Cancer Res. 1998 Feb 1;58(3):512-8
references.pmid: 9458099
references.citation: Curr Opin Immunol. 1998 Feb;10(1):103-9
references.pmid: 9523119
references.citation: Glycobiology. 1998 Jun;8(6):605-13
references.pmid: 9592127
references.citation: Biochim Biophys Acta. 1998 Jul 31;1393(1):80-9
references.pmid: 9714751
references.citation: J Biol Chem. 1998 Oct 23;273(43):28208-18
references.pmid: 9774442