title: Human fetoacinar pancreatic protein: an oncofetal glycoform of the normally secreted pancreatic bile-salt-dependent lipase.
abstract: A fetoacinar pancreatic protein (FAP) associated with the ontogenesis, differentiation and oncogenic transformation of the human exocrine pancreas has been purified from pancreatic juices of patients suffering from pancreatitis or duodenal cancers invading the pancreas [Escribano and Imperial (1989) J. Biol. Chem. 264, 21865-21871]. This protein has striking similarities, i.e. M(r), amino acid composition and N-terminal sequence, to the bile-salt-dependent lipase (BSDL) of normal human pancreatic secretion. The aim of this study was to gain further insight into the nature of the two proteins. Reactivity with the mouse monoclonal antibody J28 (mAb J28), which characterizes FAP, and enzyme activity could not be dissociated during biochemical purification of BSDL. Furthermore, a polyclonal antiserum raised against purified human BSDL reacted completely with FAP in Western-blot analysis giving additional support to the idea of similar molecular structures for BSDL and FAP. However, by the same technique, mAb J28 reacted with a relatively restricted population of BSDL molecules. The classical BSDL preparation could be separated into molecules bearing the J28 epitope and those devoid of it by immunoaffinity on immobilized mAb J28. The two subpopulations had identical N-terminal sequences and some differences in their amino acid compositions. However, they had different carbohydrate compositions. J28-epitope-bearing molecules were active on BSDL substrates, although their specific activity was decreased. These results are consistent with the existence of two closely related polypeptide chains with different glycan counterparts. Therefore, if the name FAP is reserved for molecules bearing the J28 epitope, which is linked to a carbohydrate-dependent structure. FAP could represent an oncofetal-related variant of BSDL. Our result is the first demonstration of the existence of an oncofetal-type subpopulation of an otherwise normally secreted human pancreatic enzyme.
authors.affiliation: INSERM-U.260, Faculté de Médecine, Marseille, France.
authors.forename: E
authors.initials: E
authors.lastname: Mas
authors.forename: N
authors.initials: N
authors.lastname: Abouakil
authors.forename: S
authors.initials: S
authors.lastname: Roudani
authors.forename: F
authors.initials: F
authors.lastname: Miralles
authors.forename: O
authors.initials: O
authors.lastname: Guy-Crotte
authors.forename: C
authors.initials: C
authors.lastname: Figarella
authors.forename: M J
authors.initials: MJ
authors.lastname: Escribano
authors.forename: D
authors.initials: D
authors.lastname: Lombardo
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D001647:Bile Acids and Salts / Q000494:pharmacology*; D015153:Blotting, Western; D002241:Carbohydrates / Q000032:analysis; D002352:Carrier Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D004379:Duodenal Neoplasms / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006023:Glycoproteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D008049:Lipase / Q000302:isolation & purification / Q000378:metabolism*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010189:Pancreatic Juice / Q000201:enzymology / Q000378:metabolism*; D010195:Pancreatitis / Q000378:metabolism*; D012016:Reference Values
chemical_list: D000911:Antibodies, Monoclonal; D001647:Bile Acids and Salts; D002241:Carbohydrates; D002352:Carrier Proteins; D006023:Glycoproteins; C054621:CEL protein, human; D008049:Lipase