The Chemical Basis for Expression of the Sialyl-Lea Antigen

  • David Zopf
  • Gunnar C. Hansson
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 228)


Tumor antigens can be defined by antibodies that bind cancer cells and/or their secreted products, but not cells or secreted products of normal tissues from which the cancer cells derive (1,2). Tumor antigens are of interest for three major reasons: (i) they are strategic targets for immunodiagnosis and immunotherapy; (ii) they are potential receptors mediating physiological events that determine cellular organization in tumors; (iii) they are substances produced due to altered biosynthetic control, understanding of which might provide insights into mechanisms for malignant transformation. During the past few years, several laboratories have produced monoclonal antibodies that specifically bind human cancer cells. Many of these recognize complex carbohydrate antigens (3). Such antigens sometimes are present at specific stages of normal embryonic development but disappear completely during later development or persist only in isolated, specialized tissues in the mature organism (4). Carbohydrate tumor antigens probably result from aberrant expression of glycosyltransferases that normally appear and disappear in an orderly and selective fashion according to the genetic program for histologic development and cytodifferentiation (reviewed in 5–7). the sialyl-Lea (SLea) antigen, originally defined by antibody 19–9 (8), occurs during early development in the gastrointestinal tract, but after birth is virtually absent from cells that line the stomach and intentines, persisting only in ducts and secretions of the digestive glands, respiratory tract, and reproductive system (9,10).


Blood Group Human Milk SW1116 Cell Seminal Plasma Blood Group Antigen 
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  1. 1.
    I. Damjanov and B. B. Knowles (1983) Biology of Disease: monoclonal antibodies and tumor-associated antigens, Lab. Invest. 48: 510–525.PubMedGoogle Scholar
  2. 2.
    D. J. Kennel, K. Flynn, L. Foote, and T. Lankford (1984) Monoclonal antibodies in cancer detection and therapy, Bioscience 34: 150–156.CrossRefGoogle Scholar
  3. 3.
    V. Ginsburg, J. L. Magnani, S. L. Spitalnik, P. F. Spitalnik, K. K. Roberts, and C. Dubois (1985) Carbohydrate antigens detected by monoclonal antibodies, Glycoconjugates: Proc. Vlllth Int. Symp. (Abst.), Vol 2, pp 550–551, Praeger, New York.Google Scholar
  4. 4.
    A. S. Hakomori and R. Kannagi (1983) Glycosphingolipids as tumor-assoei ated and differentiation markers, J.N.C.I. 71: 231–251.Google Scholar
  5. 5.
    S. Hakomori (1984) Tumor-associated carbohydrate antigens, Ann. Rev. Immunol. 2: 103–126.CrossRefGoogle Scholar
  6. 6.
    T. Feizi (1983) Carbohydrate differentiation antigens, Biochem. Soc. Trans. 11:263–271.PubMedGoogle Scholar
  7. 7.
    M. Fukuda (1985) Cell surface glycoconjugates as onco-differentiation markers in hematopoietic cells, Biochim. Biophys. Acta 780: 119–150.Google Scholar
  8. 8.
    H. Koprowski, Z. Steplewski, K. Mitchell, M. Herlyn, D. Herlyn, and P. Fuhrer (1979) Colorectal Carcinoma antigens detected by hybridoma antibodies, Somat. Cell Genet. 5: 957–972.PubMedCrossRefGoogle Scholar
  9. 9.
    B. F. Atkinson, C. S. Ernst, M. Herlyn, Z. Steplewski, H. F. Sears, and J. Koprowski (1982) Gastrointestinal cancer-associated antigen in immunoperoxidase assay, Cane. Res. 42; 4820–4823.Google Scholar
  10. 10.
    J. W. Arends, C. Verstynen, F. T. Bosman, J. Hilgers, and Z. Steplewski (1983) Distribution of monoclonal antibody-defined monosialoganglioside in normal and cancerous human tissues: an immunoperoxidase study, Hybridoma 2: 219–229.PubMedCrossRefGoogle Scholar
  11. 11.
    G. C. Hansson and D. Zopf (1985) Biosynthesis of the cancer-associ-ated sialyl-Lea antigen, J. Biol. Chem. 260: 9388–9392.PubMedGoogle Scholar
  12. 12.
    M. Brockhaus, M. Wysocka, J. L. Magnani, Z. Steplewski, H. Koprowski, and V. Ginsburg (1985) Normal salivary mucin contains the gastrointestinal cancer-associated antigen detected by monoclonal antibody 19–9 in the serum mucin of patients, Vox. Sang. 48: 34–38.PubMedCrossRefGoogle Scholar
  13. 13.
    H. Koprowski, M. Herlyn, Z. Steplewski, and H. F. Sears (1981) Spe cific antigen in serum of patients with colon carcinoma, Science 212: 53–55.PubMedCrossRefGoogle Scholar
  14. 14.
    J. L. Magnani, M. Brockhaus, D. F. Smith, V. Ginsburg, M. Blaszczyk, K. F. Mitchell, Z. Steplewski, and H. Koprowski (1981) A mono- sialoganglioside is a monoclonal antibody-defined antigen of colon carcinoma, Science 212: 55–56.PubMedCrossRefGoogle Scholar
  15. 15.
    J. L. Magnani, B. Nilsson, M. Brockhaus, D. Zopf, Z. Steplewski, H. Koprowski, and V. Ginsburg (1982) A monoclonal antibody-defined antigen associated with gastrointestinal cancer is a ganglioside containing sialylated lacto-N-fucopentaose II, J. Biol. Chem. 257: 14365–14369.PubMedGoogle Scholar
  16. 16.
    H. Koprowski, M. Blaszczyk, Z. Steplewski, M. Brockhaus, J. Magnani, and V. Ginsburg (1982) Lewis blood-type may affect the incidence of gastrointestinal cancer, The Lancet, June 12, 1332–1333.CrossRefGoogle Scholar
  17. 17.
    J. Picard, D. Loveday, and T. Feizi (1985) Evidence for sialylated type 1 blood group chains on human erythrocyte membranes revealed by agglutination of neuraminidase-treated erythrocytes with Waldenstrom’s macroglobulin IgMwo° and hybridoma antibody FC 10.2, Vox. Sang. 48: 26–33.PubMedCrossRefGoogle Scholar
  18. 18.
    J-M. Wieruszeski, A. Chekkor, S. Bouquelet, J. Montreuil, G. Strecker, J. Peter-Katalinic, and H. Egge (1985) Structure of two new oligosaccharides isolated from human milk: sialylated lacto-N- fucopentaoses I and II, Carb. Res. 137: 127–138.CrossRefGoogle Scholar
  19. 19.
    D. F. Smith (1985) Sialylpentasaccharides of human milk: identification by specific anti-oligosaccharide antibodies, Fed. Proc (Abst.) 44:1087.Google Scholar
  20. 20.
    F-G. Hanisch, G. Uhlenbruck, and C. Dienst (1985) Structure of tumor-associated carbohydrate antigen Ca 19–9 on human seminal-plasma glycoproteins from healthy donors, Eur. J. Biochem. 144: 467–474.CrossRefGoogle Scholar
  21. 21.
    K-E. Falk, K-A. Karlsson, G. Larson, J. Thurin, M. Blaszczyk, Z. Steplewski, and H. Koprowski (1983) Mass spectrometry of a human tumor glycolipid antigen being defined by mouse monoclonal antibody NS-19–9, Biochem. Biophys. Res. Comm. 110: 383–391.PubMedCrossRefGoogle Scholar
  22. 22.
    J-E. Mansson, P. Fredman, O. Nilsson, L. Lindholm, J. Holmgren, and L. Svennerholm (1985) Chemical structure of carcinoma ganglioside antigens defined by monoclonal antibody C-50 and some allied gangliosides of human pancreatic adenocarcinoma, Biochim. Biophys. Acta 834: 110–117.PubMedGoogle Scholar
  23. 23.
    J. L. Magnani, Z. Steplewski, H. Koprowski, and V. Ginsburg (1983) Identification of the gastrointestinal and pancreatic cancer- associated antigen detected by monoclonal antibody 19–9 in the sera of patients as a mucin, Cane. Res. 43: 5489–5492.Google Scholar
  24. 24.
    B. C. Del Villano, S. Brennan, P. Brock, C. Bucher, V. Liu, M. Mlure, B. Rake, S. Space, S. Westrick, H. Schoemaker, and V. R. Zurawski, Jr. (1983) Radioimmunometric assay for a monoclonal antibody-defined tumor marker, CA 19–9, Clin. Chem. 29: 549–552.PubMedGoogle Scholar
  25. 25.
    T. Yoshikawa, K. Nishida, M. Tanigawa, K. Fukumoto, and M. Kondo (1985) Carbohydrate antigenic determinant (CA 19–9) and other tumor markers in gastrointestinal malignancies, Digestion 31: 67–76.PubMedCrossRefGoogle Scholar
  26. 26.
    S. Hirohashi, Y. Shimosato, Y. Ino, Y. Tome, M. Watanabe, T. Hirota, and M. Itabashi (1984) Distribution of blood group antigens and CA 19–9 in gastric cancers and non-neoplastic gastric mucosa, Gann 75: 540–547.PubMedGoogle Scholar
  27. 27.
    R. R. Race and R. S. Sanger (1975) Blood Groups in Man, Blackwell, Oxford pp323–349.Google Scholar
  28. 28.
    T. Feizi, H. C. Gooi, R. A. Childs, J. K. Picard, K. Uemura, L. M. Loomes, S. J. Thorpe, and E. F. Hounsell (1984) Mucin-type glycoproteins, tumour-associated and differentiation antigens on the carbohydrate moieties of mucin-type glycoproteins, Biochem. Soc. Trans. 12: 591–596.PubMedGoogle Scholar
  29. 29.
    B. Nilsson and D. Zopf (1983) Oligosaccharides released from glycoli-pids by trifluoroacetolysis can be analyzed by gas chromatography/ mass spectrometry, Arch. Biochem. Biophys. 222: 628–648.PubMedCrossRefGoogle Scholar
  30. 30.
    W. M. Watkins and W. T. J. Morgan (1957) Specific inhibition studies relating to the Lewis blood-group system, Nature 180: 1038–1040.PubMedCrossRefGoogle Scholar
  31. 31.
    R. Kuhn, H. H. Baer, and A. Gauhe (1958) Die Konstitution der Lacto-N-fucopentaose II. Ein Beitrag zur Spezifität der Blutgruppensub- stanz Lea, Chem. Ber. 91: 364.CrossRefGoogle Scholar
  32. 32.
    R. Kuhn and A. Gauhe (1965) Bestimmung der Bindungsstelle von Sialin-säureresten in Oligosacchariden mit Hilfe von Perjodat, Chem. Ber. 98: 365.Google Scholar
  33. 33.
    M. Blaszczyk, G. C. Hansson, K.-A. Karlsson, G. Larson, N. Stromberg, J. Thurin, M. Herlyn. Z. Steplewski, and H. Koprowski (1984) Lewis blood group antigens defined by monoclonal anti-colon carcinoma antibodies, Arch. Biochem. Biophys. 233: 161–168.CrossRefGoogle Scholar
  34. 34.
    S. Hakomori and H. D. Andrews (1970) Sphingoglycolipids with Leb activity and the copresence of Lea-, Leb-active glycolipids in human tumor tissue, Biochim. Biophys. Acta 202: 225–228.PubMedGoogle Scholar
  35. 35.
    E. L. Smith, J. M. Mibbin, K.-A. Karlsson, I. Pascher, B. E. Samuelsson, Y.-T. Li, and S.-C. Li (1975) Characterization of a human intestinal fucolipid with blood group Lea activity, J. Biol. Chem. 250: 6059–6064.PubMedGoogle Scholar
  36. 36.
    O. Nilsson, J. E. Mansson, L. Lindholm, J. Holmgren, and L. Svennerholm (1985) Sialosyllactotetraosylceramide, a novel ganglioside antigen detected in human carcinomas by a monoclonal antibody, FEBS Lett. 182: 398–402.PubMedCrossRefGoogle Scholar
  37. 3.
    M. N. Fukuda, B. Bothner, K. O. Lloyd, W. J. Rettig, P. R. Tiller, and A. Dell (1986) Structures of glycosphingolipids isolated from human embryonal carcinoma cells; the presence of mono- and di- sialosyl glycolipids with blood group type 1 sequence, J. Biol. Chem. (in press).Google Scholar
  38. 38.
    W. T. J. Morgan (1960) A contribution to human biochemical genetics; the chemical basis of blood group specificity, Proc. Royal Soc. B 151: 308–347.CrossRefGoogle Scholar
  39. 39.
    E. A. Kabat (1973) Immunochemical studies on the carbohydrate moiety of water soluble blood group A, B, H, Lea, and Leb substances and their precursor I antigens, in: Carbohydrates in Solution (H. Isbell, ed.) Advances in Chemistry Series No. 117. pp 334–361, American Chemical Society, Washington, D. C.CrossRefGoogle Scholar
  40. 40.
    W. M. Watkins (1974) Genetic regulation of the structure of blood group specific glycoproteins, Biochem. Soc. Symp. 40: 125–146.PubMedGoogle Scholar
  41. 41.
    T. Mizuochi, K. Yamashita, K. Fujikawa, W. Kisiel, and A. Kobata (1979) The carbohydrate of bovine prothrombin. Occurrence of Galβl-3GlcNAc grouping in asparagine-linked sugar chains J. Biol. Chem. 254: 6419–6425.PubMedGoogle Scholar
  42. 42.
    J.-P. Prieels, K. Monnom, M. Dolmans, T. A. Beyer, and R. L. Hill (1981) Co-purification fo the Lewis blood group N-acetylglucosami- nide αl-4fucosyltransferase and an N-acetylglucosaminide αl-3fucosyl-transferase from human milk, J. Biol. Chem. 256: 10456–10463.PubMedGoogle Scholar
  43. 43.
    P. H. Johnson, A. D. Yates, and W. M. Watkins (1981) Human salivary fucosyltransferases: evidence for two distinct a-3-L-fucosyl- transferase activities one of which is associated with the Lewis blood group Le gene, Biochem. Biophys. Res. Commun. 100: 1611–1618.CrossRefGoogle Scholar
  44. 44.
    J. E. Sadler, J. I. Rearick, J. C. Paulson, and R. L. Hill (1979) Purification to homogeneity of a 3-galactoside a2–3 sialyltrans- ferase and partial purification of an a-N-acetylgalactosaminide α2–3 sialyltransferase from porcine submaxillary glands, J. Biol. Chem. 254: 4434–4443.PubMedGoogle Scholar
  45. 45.
    J. I. Rearick, J. E. Sadler, J. C. Paulson, and R. L. Hill (1979) Enzymatic characterization of (3-D-galactoside a2–3 sialyltransferase from porcine submaxillary gland, J. Biol. Chem. 254: 4444–4451.PubMedGoogle Scholar
  46. 46.
    J. Weinstein, U. de Souza-e-Silva, and J. C. Paulson (1982) Purifica tion of a Galβl-4GlcNAc α2–6 sialyltransferase and a Galβ1–3GlcNAc α2–3 sialyltransferase to homogeneity from rat liver. J. Biol. Chem. 257: 13835–13844.PubMedGoogle Scholar
  47. 47.
    J. Weinstein, U. de Souza-e-Silva, and J. C. Paulson (1982) Sialyla-tion of glycoprotein oligosaccharides N-linked to asparagine, enzymatic characterization of a Galβ1–4GlcNAc α2–3 sialyltransferase and a Galβ1–4GlcNAc α2–6 sialyltransferase from rat liver, J. Biol. Chem. 257: 13845–13851.PubMedGoogle Scholar
  48. 48.
    A.E. Szulman and D. M. Marcus (1973) The histologic distribution of the blood group substances in man as disclosed by immunofluorescence VI. The Lea and Leb antigens during fetal development, Lab. Invest. 28: 565–574.PubMedGoogle Scholar
  49. 49.
    R. Oriol, J. P. Cartron, J. Cartron, C. Mulet (1980) Biosynthesis of ABH and Lewis antigens in normal and transplanted kidney, Transplantation 29: 184–188.PubMedCrossRefGoogle Scholar
  50. 50.
    R. U. Lemieux, D. A. Baker, W. M. Weinstein, C. M. Switzer (1981) Artificial antigens: antibody preparations for the localization of Lewis determinants in tissues, Biochemistry 20: 199–205.PubMedCrossRefGoogle Scholar
  51. 51.
    C. Ernst, B. Atkinson, M. Wysocka, M. Blaszczyk, M. Herlyn, H. Sears, Z. Steplewski, and H. Koprowski (1984) Monoclonal antibody localization of Lewis antigens in fixed tissue, Lab. Invest. 50: 394–400.PubMedGoogle Scholar
  52. 52.
    H. Clausen, S. B. Levery, J. M. Mibbin, and S. Hakomori (1985) Blood group A determinants with mono- and difucosyl type 1 chain in human erythrocyte membranes, Biochemistry 24: 3578–3586.PubMedCrossRefGoogle Scholar
  53. 53.
    D. R. Roberts, D. L. Monsein, R. C. Frates, Jr., M. S. Chernick, and V. Ginsburg (1986) A serum test for cystic fibrosis using monoclonal antibody 19–9, Arch. Biochem. Biophys. 245: 292–294.CrossRefGoogle Scholar
  54. 54.
    D. Chia, P. I. Terasaki, N. Suyama, J. Galton, M. Hirota, and D. Datz (1985) Use of monoclonal antibodies to sialylated Lewix and sialylated Lewia for serological tests of cancer, Cancer Res. 45: 435–437.PubMedGoogle Scholar
  55. 55.
    W. M. Watkins and W. T. J. Morgan (1959) Possible genetical pathways for the biosynthesis of blood group mucopolysaccharides, Vox. Sang. 4: 97–119.PubMedCrossRefGoogle Scholar
  56. 56.
    V. Ginsburg (1972) Enzymatic basis for blood groups in man, Adv. Enzymol. 36: 131–149.PubMedGoogle Scholar
  57. 57.
    C. A. Tilley, M. C. Crookston, B. L. Brown, and J. R. Wherrett (1975) A and B and A1Leb substances in glycosphinglipid fractions of human serum, Vox. Sang. 28: 25–28.PubMedCrossRefGoogle Scholar
  58. 58.
    D. A. Zopf, V. Ginsburg, P. Hallgren, A.-C. Jonsson, B. S. Lindberg, and A. Lundblad (1979) Determination of Leb-active oligosaccharides in urine of pregnant and lactating women by radioimmunoassay, Eur. J. Biochem. 93: 431–435.PubMedCrossRefGoogle Scholar
  59. 59.
    T. E. Rohr, D. F. Smith, D. A. Zopf, and V. Ginsburg (1980) Leb-active glycolipid in human plasma: measurement by radioimmunoassay, Arch. Biochem. Biophys 199: 265–269.PubMedCrossRefGoogle Scholar
  60. 60.
    H. Rauvala (1976) Gangliosides of human Kidney, J. Biol. Chem. 251: 7517–7520.PubMedGoogle Scholar
  61. 61.
    E. V. Chandrasekaran, M. Davila, D. Nixon, and J. Mendicino (1984) Structures of the oligosaccharide chains of two forms of α1-acid glycoprotein purified from liver metastases of lung, colon, and breast tumors, Cancer Res. 44: 1557–1567.PubMedGoogle Scholar
  62. 62.
    P. H. Johnson and W. M. Watkins (1985) Sialyl compounds as acceptor substrates for the human α3- and α3/4-L-fucosyltransferases, Biochem. Soc. Trans. 13: 1119–1120.Google Scholar
  63. 63.
    E. H. Holmes, G. K. Ostrander, and S. Hakomori (1986) Biosyn- theisis of the sialyl-Lex determiant carried by type 2 chain gly- cosphingolipids (IV3NeuAcIII3FucnLc4, VI3NeuAcV3Fucn2Lc6, and VI3NeuAcIII3V3Fuc2nLc6) in human lung carcinoma PC9 cells, J. Biol. Chem. 261: 3737–3743.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • David Zopf
    • 1
  • Gunnar C. Hansson
    • 2
  1. 1.Laboratory of PathologyNational Cancer Institute, National Institutes of HealthBethesdaUSA
  2. 2.Department of Medical BiochemistryUniversity of GothenburgGothenburgSweden

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