Epithelial Mucin Antibodies and Their Epitopes: Core Protein Epitopes of a Polymorphic Epithelial Mucin (PEM)

  • Joyce Taylor-Papadimitriou
  • Joy Burchell
  • Sandra Gendler
  • Martina Boshell
  • Trevor Duhig


Largely because of their complexity, the detailed structure of the mucins has been difficult to analyze. This group of compounds is categorized mainly by the fact that they contain a high level of carbohydrate which is attached in O-linkage to serine and/or threonine via the linkage sugar N-acetylgalactosamine. The mucous secretions produced by some epithelial cells, particularly those lining the gastro-intestinal tract and the lungs, contain mucins along with other products and these components have been studied for some time at the biochemical level. However, other glandular epithelial cells, such as the salivary gland, breast, ovary, endometrium, and sweat glands, also produce mucins, and some of these simpler mucins have recently received much attention. This is because many antibodies selected for epithelial or tumor specificity have been found to react with high molecular weight glycoproteins which are produced by simple epithelial cells and have the properties of mucins.1–9


Core Protein Potential Glycosylation Site Plasmodium Knowlesi High Molecular Weight Glycoprotein Oligosaccharide Side Chain 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    J. Burchell, H. Durbin and J. Taylor-Papadimitriou, Complexity of expression of antigenic determinants recognised by monoclonal antibodies HMFG-1 and HMFG-2, in normal and malignant human mammary epithelial cells, J. Immunol. 131:508 (1983).PubMedGoogle Scholar
  2. 2.
    J. Burchell, S. Gendler, J. Taylor-Papadimitriou, A. Girling, A. Lewis, R. Millis and D. Lamport, Development and characterization of breast cancer reactive monoclonal antibodies directed to the core protein of the human milk mucin, Cancer Res. 47:5476 (1987).PubMedGoogle Scholar
  3. 3.
    A. B. Griffiths, J. Burchell, J. Taylor-Papadimitriou, S. Gendler, A. Lewis, K. Blight and R. Tilly, Immunological analysis of mucin molecules expressed by normal and malignant mammary epithelial cells, Int. J. Cancer 40:319 (1987).PubMedCrossRefGoogle Scholar
  4. 4.
    H. Sekine, T. Ohno and D. Kufe, Purification and characterization of a high molecular weight glycoprotein detectable in human milk and breast carcinomas, J. Immunol. 135:3610 (1985).PubMedGoogle Scholar
  5. 5.
    J. Hilkens, F. Buijs, J. Hilgers, P. Hagemann, J. Calafat, A. Sonnenberg, and M. Van der Valk, Monoclonal antibodies against human milk fat globule membranes detecting differentiation antigens of the mammary gland and its tumour, Int. J. Cancer 34:197 (1984).PubMedCrossRefGoogle Scholar
  6. 6.
    C. Foster, P.A. Edwards, E.A. Dinsdale and A.M. Neville, Monoclonal antibodies to the human mammary gland. I. Distribution of determinants in non-neoplastic mammary and extra mammary tissues Virchows Arch. (Path. Anat.) 394:279 (1982).CrossRefGoogle Scholar
  7. 7.
    M. Price, S. Edwards, A. Owainati, J.E. Bullock, B. Ferry, R.A. Robins and R.W. Baldwin, Multiple epitopes on a human breast carcinoma associated antigen, Int. J. Cancer 36:567 (1985).PubMedCrossRefGoogle Scholar
  8. 8.
    R. L. Ceriani, J. A. Peterson, J. Y. Lee, R. Moncada and E. W. Blank, Characterisation of cell surface antigens of human mammary epithelial cells with monoclonal antibodies prepared against human milk fat globule, Som. Cell Genet. 9:415 (1983).CrossRefGoogle Scholar
  9. 9.
    M.E. Bramwell, V.P. Bhavanandan, G. Wiseman, and H. Harris, Structure and function of the Ca antigen, Br. J. Cancer 48:177 (1983).PubMedCrossRefGoogle Scholar
  10. 10.
    S. J. Gendler, J. M Burchell, T. Duhig, D. Lamport, R. White, M. Parker and J. Taylor-Papadimitriou, Cloning of partial cDNA encoding differentiation and tumor-associated mucin glycoproteins expressed by human mammary epithelium, Proc. Natl. Acad. Sci. USA. 84:6060 (1987).PubMedCrossRefGoogle Scholar
  11. 11.
    B. Griffiths, A. Gordon, J. Burchell, M. Bramwell, A. Griffiths, M. Price, J. Taylor-Papadimitriou, D. Zanin, and D.M. Swallow, The breast tumour-associated epithelial mucins and the peanut lectin binding urinary mucins are coded by a single highly polymorhpic gene locus ‘PUM’, Dis. Markers 6:185 (1988).PubMedGoogle Scholar
  12. 12.
    S. Gendler, J. Taylor-Papadimitriou, T. Duhig, J. Rothbard, and J. Burchell, A highly immunogenic region of a human polymorphic epithelial mucin expressed by carcinomas is made up of tandem repeats, J. Biol. Chem. 263:12820 (1988).PubMedGoogle Scholar
  13. 13.
    M. Shimizu and K. Yamauchi, Isolation and characterisation of mucin-like glycoproteins in human milk fat globule membranes. J. Biochem. 91:515 (1982).PubMedGoogle Scholar
  14. 14.
    J. Burchell, and J. Taylor-Papadimitriou, Antibodies to human milk fat globule molecules, Cancer Invest. (in press).Google Scholar
  15. 15.
    S.A. Bader and H. Harris, Regulation of epitectin production in a malignant cell line, J. Cell Sci. 87:375 (1987).PubMedGoogle Scholar
  16. 16.
    E. Heyderman, K. Steele, and M.G. Ormerod, A new antigen on the epithelial membrane: Its immunoperoxidase localization in normal and neoplastic tissues, J. Clin. Pathol. 32:35 (1979).PubMedCrossRefGoogle Scholar
  17. 17.
    D.M. Swallow, S. Gendler, B. Griffiths, G. Corney, J. Taylor-Papadimitriou, and M.E. Bramwell, The human tumour-associated epithelial mucins are coded by an expressed hypervariable gene locus PUM, Nature 328:82 (1987).PubMedCrossRefGoogle Scholar
  18. 18.
    D. Swallow, S. Gendler, B. Griffiths, A. Kearney, S. Povey, D. Sheer, R. Palmer and J. Taylor-Papadimitriou, The hypervariable gene locus PUM, which codes for the tumour associated epithelial mucins, is located on chromosome 1, within the region 1q21–24, Ann. Hum. Genet. 51:289 (1987).PubMedCrossRefGoogle Scholar
  19. 19.
    J.M. Trent, Cytogenetic and molecular biologic alterations in human breast cancer: a review, Breast Can. Res. & Treatment 5:221 (1985).CrossRefGoogle Scholar
  20. 20.
    N.B. Atkins, Chromosome 1 aberrations in cancer, Cancer Genet. Cytogenet. 21:279 (1986).CrossRefGoogle Scholar
  21. 21.
    E. Gebhart, S. Bruderlein, M. Augustus, E. Siebert, J. Feldner, and W. Schmidt, Cytogenetic studies on human breast carcinomas. Br. J. Cancer Res. & Treatment 8:125 (1986).CrossRefGoogle Scholar
  22. 22.
    P. Walter, S. Green, Greene G., A. Krust, J.-M. Bornert, J.-M. Heltsch, A. Staub, E. Jensen, G. Scrace, M. Waterfield and P. Chambon, Cloning of the human estrogen receptor cDNA. Proc. Natl. Acad. Sci. USA. 82:7889 (1985).PubMedCrossRefGoogle Scholar
  23. 23.
    J. Siddiqui, M. Abe, D. Hayes, E. Shani, E. Yunis, and D. Kufe, Isolation and sequencing of a cDNA coding for the human DF3 breast carcinoma-associated antigen, Proc. Natl. Acad. Sci. USA. 85:2320 (1988).PubMedCrossRefGoogle Scholar
  24. 24.
    C.S. Timpte, A.E. Eckhardt, J.L. Abernethy, and R.L. Hill, Porcine submaxillary gland apomucin contains tandemly repeated, identical sequences of 81 residues, J. Biol. Chem. 263:1081 (1988).PubMedGoogle Scholar
  25. 25.
    A. Wesley, M. Mantle, D. Man, R. Quereshi, G. Forstner and J. Forstner, Neutral and acidic species of human intestinal mucin, J. Biol. Chem. 260:7955 (1985).PubMedGoogle Scholar
  26. 26.
    J.R. Clamp, A. Allen, R.A. Gibbons and G.P. Roberts, Chemical aspects of mucins, Br. Med. Bull. 34:25 (1978).PubMedGoogle Scholar
  27. 27.
    R.L. Shogrun, A.M. Jamieson, J. Blackwell and N. Jentoft, The thermal depolymerisation of porcine submaxillary mucin, J. Biol. Chem. 259:14657, 1984.Google Scholar
  28. 28.
    M.A.T. Muskavitch, and D.S. Hogness, An expandable gene that encodes a drosophila glue protein is not expressed in variants lacking remote upstream sequences, Cell 29:1041 (1982).PubMedCrossRefGoogle Scholar
  29. 29.
    R.F. Manning and I.P. Gage, Internal structure of the silk fibroin gene of bombyx mori. II. Remarkable polymorphism of the organization of crystalline and amorphous coding sequences. J. Biol. Chem. 255:9451 (1980).PubMedGoogle Scholar
  30. 30.
    J.G. Williams, A. Ceccarelli, S. McRobbie, H. Mahbubani, R.R. Kay, A. Early, M. Berks, and K.A. Jermyn, Direct induction of dictyostelium prestalk gene expression by DIF provides evidence that DIF is a morphogen, Cell 49:185 (1987).PubMedCrossRefGoogle Scholar
  31. 31.
    L.S Ozaki, P. Svec, R.S. Nussenzweig, V. Nussenzweig, and G.N. Godson, Structure of the plasmodium knowlesi gene coding for the circumsporozoite protein, Cell 39:815 (1983).CrossRefGoogle Scholar
  32. 32.
    G.N. Godson, J. Ellis, P. Svec, D.H. Schlesinger, and V. Nussenzweig, Identification and chemical synthesis of a tandemly repeated immuogenic region of Plasmodium knowlesi circumsporozoite protein. Nature 305:29 (1983).PubMedCrossRefGoogle Scholar
  33. 33.
    R.L. Eckert, and H. Green, Structure and evolution of the human involucrin gene, Cell 46:583 (1986).PubMedCrossRefGoogle Scholar
  34. 34.
    J. Taylor-Papadimitriou, J.A. Peterson, J. Arklie, J. Burchell, R.L. Ceriani, and W.F. Bodmer, Monoclonal antibodies to epithelium-specific components of the human milk fat globule membrane: production and reaction with cells in culture, Int. J. Cancer 28:17 (1981).PubMedCrossRefGoogle Scholar
  35. 35.
    F.-G. Hanisch, G. Uhlenbruck, J. Peter-Katalinic, H. Egge, J. Dabrowski, and U. Dabrowski, Structures of neutral 0-linked polylactosaminoglycans on human skim milk mucins, J. Biol. Chem. (in press).Google Scholar
  36. 36.
    F.-G. Hanisch, G. Uhlenbruck, C. Dienst, M. Stottrop and E. Hippauf, Ca125 and Ca19–9: two cancer-associated sialylsaccharide antigens on a mucus glycoprotein from human milk, Eur. J. Biochem. 149:323 (1985).PubMedCrossRefGoogle Scholar
  37. 37.
    S.R. Hull, A. Bright, K.L. Carraway, M. Abe, and D. Kufe, Oligosaccharides of the DF-3 antigen of the BT20 human breast carcinoma cell line, J. Cell. Biochem. Suppl. 12E:130 (1988).Google Scholar
  38. 38.
    D. Colcher, P. Horan Hand, M. Nuti and J. Schlom, Production of monoclonal antibodies reactive with human mammary carcinomas, Proc. Natl. Acad. Sci. USA. 78:3199 (1981).PubMedCrossRefGoogle Scholar
  39. 39.
    T. Kjeldsen, H. Clausen, S. Hirohashi, T. Ogawa, H. Iijima and S. Hakomori, Preparation and characterization of monoclonal antibodies directed to the tumour associated O-linked sialosyl-2→6 α-N-acetylgalactosaminyl (Sialosyl-Tn) epitope, Cancer Res. 48:2214 (1988).PubMedGoogle Scholar
  40. 40.
    H.K. Takahashi, R. Metoki and S. Hakomori, Immunoglobulin G3 monoclonal antibody directed to Tn antigen (tumor-associated α-N-acetylgalactosaminyl epitope) that does not cross-react with blood group A antigen, Cancer Res. 48:4361 (1988).PubMedGoogle Scholar
  41. 41.
    A.J. Leathem and S.A. Brooks, Predictive value of lectin binding on breast-cancer recurrence and survival, The Lancet May 9:1054 (1987).CrossRefGoogle Scholar
  42. 42.
    A. Kurosaka, S. Fukui, H. Kitagawa, H. Nakada, Y. Numata, I. Funakoshi, T. Kawasaki and I. Yamashina, Mucin-carbohydrate directed monoclonal antibody, FEBS Lett. 215:137 (1987).PubMedCrossRefGoogle Scholar
  43. 43.
    J. Magnani, B. Nilsson, M. Brockhaus, D. Zopf, Z. Steplewski, H. Koprowski and V. Ginsburg, A monoclonal antibody-defined antigen associated with gastrointestinal cancer is a ganglioside containing sialylated lacto-N-fucopentaose II, J. Biol. Chem. 257:14365 (1982).PubMedGoogle Scholar
  44. 44.
    D. Chia, P.I. Terasaki, N. Suyama, J. Galton, M. Hirota and S. Katz, Use of monoclonal antibodies to sialylated Lewis and sialylated Lewis for serological tests of cancer, Cancer Res 45:435 (1985).PubMedGoogle Scholar
  45. 45.
    R.C. Bast Jr., T.L. Klug, E. St. John, E. Jenison, J.M. Niloff, H. Lazarus, R.S. Berkowitz, T. Leavitt, C.T. Griffiths, L. parker, V.R. Zurawski and R.C. Knapp, A radioimmunoassay using a monoclonal antibody to monitor the course of epithelial ovarian cancer, N. Eng. J. Med. 309:883 (1983).CrossRefGoogle Scholar
  46. 46.
    C. Foster, and A.M. Neville, Monoclonal antibodies to the human mammary gland. III. Monoclonal antibody LICR-L0N-M18 identifies impaired expression and excess sialylation of the 1(Ma) cell surface antigen by primary breast carcinoma cells, Hum. Pathol. 15:82 (1984).CrossRefGoogle Scholar
  47. 47.
    J.L. Magnani, Z. Steplewski, H. Koprowski and V. Ginsburg, Identification of the gastrointestinal and pancreatic cancer-associated antigen detected by monoclonal antibody 19.9 in the sera of patients as a mucin, Cancer Res. 43:5489 (1983).PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1989

Authors and Affiliations

  • Joyce Taylor-Papadimitriou
    • 1
  • Joy Burchell
    • 1
  • Sandra Gendler
    • 1
  • Martina Boshell
    • 1
  • Trevor Duhig
    • 1
  1. 1.Imperial Cancer Research FundLondonUK

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