Skip to main content
Log in

Analysis of the lewisx epitope in human pancreas and pancreatic adenocarcinomas

  • Published:
International journal of pancreatology Aims and scope Submit manuscript

Summary

The Lewisx epitope (Gal²l-4[Fucal-3]GlcNAc-R) can be detected in most ductal pancreatic carcinomas. However, few data pertain to its expression in normal exocrine pancreas and its biochemistry. We compared the expression of the Lewisx epitope in normal pancreas with its expression in pancreatic adenocarcinomas and tumor cell lines and to further characterize the nature of the antigens bearing this epitope with immunochemical methods. On frozen tissue sections of normal pancreas, the Lewisx epitope was detected focally in acinar cell granules; sialosyl-Lewisx was detected in centroacinar cells and the cytoplasm of intralobular ducts. Sixteen of 19 pancreatic carcinomas expressed the Lewisx antigen on tissue sections; however, there was no correlation with prognostic parameters, such as tumor grade or stage. Eighteen of 19 tumor specimens were positive for sialosyl-Lewisx. Analysis of pancreatic carcinoma cell lines (CAPAN-1, CAPAN-2, and DAN-G) revealed intracytoplasmic expression of sialosyl-Lewisx epitopes in these cells, and cell surface reactivity was detected on flow cytometry for sialosyl-Lewisx. Lectin-affinity chromatography of cytoplasmac preparations showed that Lewisx-positive antigens of normal human pancreas bind to SB A and UEA-I lectins but have little or no affinity to WGA, GS-I, or DBA lectins, indicating the presence of Fuc and Gal oligosaccharide residues. It was concluded that the Lewisx and sialosyl-Lewisx antigens are nonpolymorphic carbohydrate determinants that are present in secretory granules of acinar cells, ductules, and pancreatic secretions. This makes the Lewisx antigen suitable for the analysis of the secretory process in the exocrine pancreas and the study of secretory differentiation antigens in ductal pancreatic carcinoma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Coon JS Weinstein RS. Blood group related antigens as markers of malignant potential and heterogeneity in human carcinomas.Hum Pathol 1986; 17:1089–1106.

    Article  PubMed  CAS  Google Scholar 

  2. Itzkowitz SH Kim YS. New carbohydrate tumor markers.Gastroenterology 1989; 90: 491–493.

    Google Scholar 

  3. Itzkowitz SH, Yuan M, Ferell LD, Ratcliffe RM, Chuan YS, Satake K, Umeyama K, Jones RT, and Kim YS. Cancerassociated alterations of blood group antigen expression in the human pancreas.J Natl Cancer Inst 1987; 79:425–434.

    PubMed  CAS  Google Scholar 

  4. Haglund C, Lindgren J, Roberts PJ, and Nordling S. Gastrointestinal cancer-associated antigen CA 19-9 in histological specimens of pancreatic tumours and pancreatitis.Br J Cancer 1986; 53:189–195.

    PubMed  CAS  Google Scholar 

  5. Magnani JL, Nilsson B, Brockhaus M, Zopf D, Speplewski Z, Koprowski H, Ginsburg V. A monoclonal antibodydefined antigen associated with gastrointestinal cancer is a ganglioside containing sialylated lacto-N-fucopentaose II.J Biol Chem 1982; 257: 1436–4369

    Google Scholar 

  6. Kim YS, Itzkowitz SH, Yuan M, Chung YS, Satake K, Umeyama K, and Hakomori S. Lewisx and Lewisy antigen expression in human pancreatic cancer.Cancer Res 1988; 48: 475–482.

    PubMed  CAS  Google Scholar 

  7. Rouger P, Goossens D, Gane P, and Salmon C. Distribution of blood group antigens in adult pancreas.Tissue Antigens 1987;18: 51–55.

    Google Scholar 

  8. Mollicone R, Bnara J, LePendu J, and Oriol R. Immunohistologic pattern of type 1 (Lewisa, Lewisb) and type 2 (X, Y, H) blood group related antigens in the human pyloric and duodenal mucosae.Lab Invest 1985; 53: 219–227.

    PubMed  CAS  Google Scholar 

  9. Sakamoto J, Furukawa K, Cordon-Cardo C, Yin BWT, Rettig WJ, Oettgen HF, Old LJ, and Lloyd KO. Expression of Lewisa, Lewisb, X, and Y blood group antigens in human colonic tumors and normal tissue and in human tumorderived cell lines.Cancer Res 1986; 46:1553–1561.

    PubMed  CAS  Google Scholar 

  10. Kannagi R, Fukushi Y, and Tachikawa T. Quantitative and qualitative characterization of human cancer-associated serum glycoprotein antigens expressing fucosyl or sialylfucosyl type 2 chain polylactosarnine.Cancer Res 1986; 46: 2619–2626.

    PubMed  CAS  Google Scholar 

  11. Kumazaki T and Yoshida A. Biochemical evidence that the secretor gene, Se, is a structural gene encoding a specific fucosyltransferase.Proc Natl Acad Sci USA 1984; 81: 4193–4197.

    Article  PubMed  CAS  Google Scholar 

  12. Watkins WM. Biochemistry and genetics of the ABO, Lewis and P blood group systems.Adv. Hum. Genetics 1980,10:1–136.

    CAS  Google Scholar 

  13. Blaszczyk M,Pak KY, Herlyn M, Sears HF, and Steplewski Z. Characterization of Lewis antigens in normal colon and gastrointestinal adenocarcinomas.Proc Natl Acad Sci USA 1985;82: 3552–3556.

    Article  PubMed  CAS  Google Scholar 

  14. Ernst C, Atkinson B, Wysocka M, Blaszczyk M, Herlyn M, Sears H, Steplewski Z, and Koprowski H. Monoclonal antibody localization of Lewis antigens in fixed tissue.Lab Invest 1984; 50: 394–400.

    PubMed  CAS  Google Scholar 

  15. Sakamoto J, Yin BWT, and Lloyd KO. Analysis of the expression of H, Lewis, X, Y, and precursor blood group determinants in saliva and red cells using a panel of mouse monoclonal antibodies.Mollmmunol 1984; 21:1093–1098.

    CAS  Google Scholar 

  16. Fox G, Damjanov I, Knowles BB, and Solter D. Immunohistochemical localization of the mouse stage-specific embryonic antigen 1 in human tissues and tumors.Cancer Res 1983; 43: 669–678.

    PubMed  CAS  Google Scholar 

  17. Rettig WJ, Cordon-Carlo C, Ng JSC, Oettgen HF, Old LJ, and Lloyd KO. High-molecular-weight glycoproteins of human teratocarcinoma defined by monoclonal antibodies to carbohydrate determinants.Cancer Res 1985; 45: 815–821.

    PubMed  CAS  Google Scholar 

  18. Sanders DSA, Coghill G, and Kerr MA. Detection of differences in the specificity of the CD15 monoclonal antibody panel by immunohistochemical staining of squamous epithelia and lymph nodes.Tissue Antigens 1989; 33:218, (Abstract).

    Article  Google Scholar 

  19. Thompson JS, Goeken NE, and Brown SA. Antigens common to monocytes and endothelial cells: Detection by monoclonal antibodies. Advances in Immunobiology: Blood Cell Antigens and Bone Marrow Transplantation, McCullogh J, ed., Alan Liss Inc., New York, 1984; 169–187.

    Google Scholar 

  20. Thompson JS, Brown SA, Rhoades JL, Burch J, Oberle EM, Jezek DA, Jennings CD, and Sinn HP. G10F5 (workshop no. 310), reacts with pronase resistant epitope whose tissue distribution differs from CD 15 monoclonal antibodies. Leukocyte Typing III, McMicheal AJ, ed., Oxford University, Oxford, 1987; 713–716.

    Google Scholar 

  21. Symington FW, McMasterBE, Hakomori S, and Bernstein ID. Glycolipid specificities of anti-hematopoietic cell antibodies. Leukocyte Typing II, Reinherz EL, Haynes BF, Nadler LM, and Bernstein ID., ds., Springer-Verlag, New York, 1985; vol 3, p. 47–54.

    Google Scholar 

  22. Huang LC, Brockhaus M, Magnani JL, Cuttitta F, Rosen S, Minna JD, and Ginsburg V. Many monoclonal antibodies with an apparent specificity for certain lung cancers are directed against a sugar sequence found in Lacto-N-fucopentaose III.Arch Biochem Biophys 1983; 220:318–320.

    Article  PubMed  CAS  Google Scholar 

  23. Hsu SM, Raine L, and Fanger H. The use of avidin-biotinperoxidase (ABS) in immunoperoxidase techniques. A comparison beteen ABC and unlabeled antibody (PAP) procedures.J Histochem Cytochem 1981; 29: 577–580.

    PubMed  CAS  Google Scholar 

  24. Kobata A Ginsburg V. Oligosaccharides of human milk. II. Isolation and characterization of a new pentasaccharide, Lacto-W-fucopentaose IK Biol Chem 1969; 241: 5496–5502.

    Google Scholar 

  25. Yang H Hakomori S. A sphingolipid having a novel type of ceramide and Lacto-N-fucopentaose III.J Biol Chem 1971; 246:1192–1200.

    PubMed  CAS  Google Scholar 

  26. Urdal DL, Brentnall TA, Bernstein ID, and Hakomori S. A granulocyte reactive monoclonal antibody, 1G10, identifies the βGall : 4[αFucl: 3]j3GlcNAc (X Determinant) expressed in HL-60 cells on both glycolipid and glycoprotein molecules.Blood 1983; 62:1022–1026.

    PubMed  CAS  Google Scholar 

  27. Huang LC, Civin CI, Magnani JL, Shaper JH, and Ginsburg V. My-1, the human myeloid-specific antigen detected by mouse monoclonal antibodies, is a sugar sequence found in Lacto-N-fucopentaose III.Blood 1983; 61: 1020–1023.

    PubMed  CAS  Google Scholar 

  28. Itzkowitz SH, Yuan M, Fukushi Y, Palekar A, Phelps PC, Shamusuddin AM, Trump BF, Hakomori S, and Kim YS. Lewisx- and sialylated Lewisx-related antigen expression in human malignant and nonmalignant colonic tissues.Cancer Res 1986; 46: 2627–2632.

    PubMed  CAS  Google Scholar 

  29. Brockhaus M, Magnani JL, and Herlyn M. Monoclonal antibodies directed against the sugar sequence of lacto-N- fucopentaose III are obtained from mice immunized with human tumors.J Biol Chem 1982; 251: 2385–2387.

    Google Scholar 

  30. Solter D Knowles BB. Monoclonal antibody defining a stage-specific mouse embryonic antigen (SSEA-1).Proc Natl Acad Sci USA 1978; 75: 5565–5569.

    Article  PubMed  CAS  Google Scholar 

  31. Hakomori S, Nudelmann E, Levery S, Solter D, Knowles B. The hapten structure of a developmentally regulated glycolipid antigen (SSEA-1) isolated from human erythrocytes and adenocarcinomas: A preliminary note. Biochem.Biophys Res Comm 1981;100: 1578–1586.

    Article  PubMed  CAS  Google Scholar 

  32. Reddy JK, Reddy M, Hansen LJ, and Qureshi S A. Secretion granules of transpl an table pancreatic acinar carcinoma of the rat.Biochem J 1980; 188: 921–924.

    PubMed  CAS  Google Scholar 

  33. Morohoshi T, Kanda M, Horie A, Chott A, Dreyer T, Klöppel A, Heitz PU. Immunocytochemical markers of uncommon pancreatic tumors.Cancer 1987; 59: 739–747.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sinn, HP., Brown, S.A., Oherle, E. et al. Analysis of the lewisx epitope in human pancreas and pancreatic adenocarcinomas. Int J Pancreatol 11, 125–135 (1992). https://doi.org/10.1007/BF02925984

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02925984

Key Words

Navigation