Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1993 Jan 15;289(Pt 2):609–615. doi: 10.1042/bj2890609

Human fetoacinar pancreatic protein: an oncofetal glycoform of the normally secreted pancreatic bile-salt-dependent lipase.

E Mas 1, N Abouakil 1, S Roudani 1, F Miralles 1, O Guy-Crotte 1, C Figarella 1, M J Escribano 1, D Lombardo 1
PMCID: PMC1132213  PMID: 8424803

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.

Full text

PDF
609

Images in this article

611Figure 2
on p.611

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abouakil N., Lombardo D. Inhibition of human milk bile-salt-dependent lipase by boronic acids. Implication to the bile salts activator effect. Biochim Biophys Acta. 1989 Aug 8;1004(2):215–220. doi: 10.1016/0005-2760(89)90270-1. [DOI] [PubMed] [Google Scholar]
  2. Abouakil N., Rogalska E., Bonicel J., Lombardo D. Purification of pancreatic carboxylic-ester hydrolase by immunoaffinity and its application to the human bile-salt-stimulated lipase. Biochim Biophys Acta. 1988 Aug 12;961(3):299–308. doi: 10.1016/0005-2760(88)90077-x. [DOI] [PubMed] [Google Scholar]
  3. Aho H. J., Sternby B., Kallajoki M., Nevalainen T. J. Carboxyl ester lipase in human tissues and in acute pancreatitis. Int J Pancreatol. 1989 Sep;5(2):123–134. doi: 10.1007/BF02924413. [DOI] [PubMed] [Google Scholar]
  4. Albers G. H., Escribano M. J., Gonzalez M., Mulliez N., Nap M. Fetoacinar pancreatic protein in the developing human pancreas. Differentiation. 1987;34(3):210–215. doi: 10.1111/j.1432-0436.1987.tb00068.x. [DOI] [PubMed] [Google Scholar]
  5. Benedi V. J., Escribano M. J., Zuinghedau J., Burtin P. Fetal pancreatic antigens in the Syrian golden hamster and their relationship to development and carcinogenesis. Cancer Res. 1984 Mar;44(3):1135–1141. [PubMed] [Google Scholar]
  6. Blind P. J., Bläckberg L., Hernell O., Ljungberg B. Carboxylic ester hydrolase: a serum marker of acute pancreatitis. Pancreas. 1987;2(5):597–603. [PubMed] [Google Scholar]
  7. Burnette W. N. "Western blotting": electrophoretic transfer of proteins from sodium dodecyl sulfate--polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein A. Anal Biochem. 1981 Apr;112(2):195–203. doi: 10.1016/0003-2697(81)90281-5. [DOI] [PubMed] [Google Scholar]
  8. Carré-Llopis A., Escribano M. J. Isolation and characterization of two oncofetal glycoproteins from hamster pancreas using concanavalin A and preparative electrophoresis. Biochim Biophys Acta. 1986 Feb 19;880(2-3):101–107. doi: 10.1016/0304-4165(86)90068-1. [DOI] [PubMed] [Google Scholar]
  9. Cornish-Bowden A. Assessment of protein sequence identity from amino acid composition data. J Theor Biol. 1977 Apr 21;65(4):735–742. doi: 10.1016/0022-5193(77)90019-4. [DOI] [PubMed] [Google Scholar]
  10. DiPersio L. P., Fontaine R. N., Hui D. Y. Identification of the active site serine in pancreatic cholesterol esterase by chemical modification and site-specific mutagenesis. J Biol Chem. 1990 Oct 5;265(28):16801–16806. [PubMed] [Google Scholar]
  11. Eriguchi M., Carré-Llopis A., Orbach-Arbouys S., Escribano J. Evolution of the expression of fetal acinar antigens during carcinogenesis of the pancreas in hamsters: individual follow-up by open biopsy. J Natl Cancer Inst. 1987 Mar;78(3):519–525. [PubMed] [Google Scholar]
  12. Erlanson C. p-nitrophenylacetate as a substrate for a carboxyl-ester hydrolase in pancreatic juice and intestinal content. Scand J Gastroenterol. 1970;5(5):333–336. [PubMed] [Google Scholar]
  13. Escribano M. J., Carré-Llopis A., Loridon-Rosa B. Expression of oncofoetal pancreatic antigens in hamster adult pancreas during experimental carcinogenesis. Br J Cancer. 1985 Feb;51(2):187–193. doi: 10.1038/bjc.1985.28. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Escribano M. J., Cordier J., Nap M., Ten Kate F. J., Burtin P. Differentiation antigens in fetal human pancreas. Reexpression in cancer. Int J Cancer. 1986 Aug 15;38(2):155–160. doi: 10.1002/ijc.2910380202. [DOI] [PubMed] [Google Scholar]
  15. Escribano M. J., Imperial S. Purification and molecular characterization of FAP, a feto-acinar protein associated with the differentiation of human pancreas. J Biol Chem. 1989 Dec 25;264(36):21865–21871. [PubMed] [Google Scholar]
  16. Freed L. M., York C. M., Hamosh M., Sturman J. A., Hamosh P. Bile salt-stimulated lipase in non-primate milk: longitudinal variation and lipase characteristics in cat and dog milk. Biochim Biophys Acta. 1986 Sep 12;878(2):209–215. doi: 10.1016/0005-2760(86)90148-7. [DOI] [PubMed] [Google Scholar]
  17. Fujii Y., Albers G. H., Carre-Llopis A., Escribano M. J. The diagnostic value of the foetoacinar pancreatic (FAP) protein in cancer of the pancreas; a comparative study with CA19/9. Br J Cancer. 1987 Oct;56(4):495–500. doi: 10.1038/bjc.1987.232. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gjellesvik D. R., Lombardo D., Walther B. T. Pancreatic bile salt dependent lipase from cod (Gadus morhua): purification and properties. Biochim Biophys Acta. 1992 Mar 4;1124(2):123–134. doi: 10.1016/0005-2760(92)90088-d. [DOI] [PubMed] [Google Scholar]
  19. Guy-Crotte O., Barthe C., Basso D., Fournet B., Figarella C. Characterization of two glycoproteins of human pancreatic juice: P35, a truncated protease E and P19, precursor of protein X. Biochem Biophys Res Commun. 1988 Oct 14;156(1):318–322. doi: 10.1016/s0006-291x(88)80842-8. [DOI] [PubMed] [Google Scholar]
  20. Guy O., Lombardo D., Brahms J. G. Structure and conformation of human pancreatic carboxyl-ester hydrolase. Eur J Biochem. 1981 Jul;117(3):457–460. doi: 10.1111/j.1432-1033.1981.tb06360.x. [DOI] [PubMed] [Google Scholar]
  21. Han J. H., Stratowa C., Rutter W. J. Isolation of full-length putative rat lysophospholipase cDNA using improved methods for mRNA isolation and cDNA cloning. Biochemistry. 1987 Mar 24;26(6):1617–1625. doi: 10.1021/bi00380a020. [DOI] [PubMed] [Google Scholar]
  22. Kang E. Y., Coleman R. D., Pownall H. J., Gotto A. M., Jr, Yang C. Y. Analysis of the carbohydrate composition of glycoproteins by high-performance liquid chromatography. J Protein Chem. 1990 Feb;9(1):31–35. doi: 10.1007/BF01024981. [DOI] [PubMed] [Google Scholar]
  23. Kyger E. M., Wiegand R. C., Lange L. G. Cloning of the bovine pancreatic cholesterol esterase/lysophospholipase. Biochem Biophys Res Commun. 1989 Nov 15;164(3):1302–1309. doi: 10.1016/0006-291x(89)91811-1. [DOI] [PubMed] [Google Scholar]
  24. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  25. Lombardo D., Guy O. A rapid and convenient colorimetric assay for cholesterol ester hydrolase activity. Biochimie. 1979;61(3):415–417. doi: 10.1016/s0300-9084(79)80135-2. [DOI] [PubMed] [Google Scholar]
  26. Lombardo D., Guy O., Figarella C. Purification and characterization of a carboxyl ester hydrolase from human pancreatic juice. Biochim Biophys Acta. 1978 Nov 10;527(1):142–149. doi: 10.1016/0005-2744(78)90263-2. [DOI] [PubMed] [Google Scholar]
  27. Matsuura H., Greene T., Hakomori S. An alpha-N-acetylgalactosaminylation at the threonine residue of a defined peptide sequence creates the oncofetal peptide epitope in human fibronectin. J Biol Chem. 1989 Jun 25;264(18):10472–10476. [PubMed] [Google Scholar]
  28. Moorman A. F., De Boer P. A., Evans D., Charles R., Lamers W. H. Expression patterns of mRNAs for alpha-fetoprotein and albumin in the developing rat: the ontogenesis of hepatocyte heterogeneity. Histochem J. 1990 Dec;22(12):653–660. doi: 10.1007/BF01047449. [DOI] [PubMed] [Google Scholar]
  29. Patton J. S., Warner T. G., Benson A. A. Partial characterization of the bile salt-dependent triacylglycerol lipase from the leopard shark pancreas. Biochim Biophys Acta. 1977 Feb 23;486(2):322–330. doi: 10.1016/0005-2760(77)90028-5. [DOI] [PubMed] [Google Scholar]
  30. Reue K., Zambaux J., Wong H., Lee G., Leete T. H., Ronk M., Shively J. E., Sternby B., Borgström B., Ameis D. cDNA cloning of carboxyl ester lipase from human pancreas reveals a unique proline-rich repeat unit. J Lipid Res. 1991 Feb;32(2):267–276. [PubMed] [Google Scholar]
  31. Scheele G., Bartelt D., Bieger W. Characterization of human exocrine pancreatic proteins by two-dimensional isoelectric focusing/sodium dodecyl sulfate gel electrophoresis. Gastroenterology. 1981 Mar;80(3):461–473. [PubMed] [Google Scholar]
  32. Wang C. S., Martindale M. E., King M. M., Tang J. Bile-salt-activated lipase: effect on kitten growth rate. Am J Clin Nutr. 1989 Mar;49(3):457–463. doi: 10.1093/ajcn/49.3.457. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES