Breast Mucin and Associated Antigens in Diagnosis and Therapy

  • Jerry A. Peterson
  • Roberto L. Ceriani
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 353)


The human milk fat globule (HMFG) membrane has been the source of antigens for the production of polyclonal and monoclonal antibodies against normal and malignant breast epithelial cells that have found important applications in diagnosis and therapy of breast cancer (Ceriani et al., 1977). Monoclonal antibodies (MoAbs) prepared against the HMFG membrane, for the first time, identified a highly glycosylated, large molecular weight glycoprotein (breast mucin) as a major component of the surface membrane of breast epithelial cells (Ceriani et al, 1983). In addition, MoAbs against smaller glycoproteins of the HMFG have identified new and potentially important components of breast epithelial cell membranes, namely two glycoproteins of 70 kDa and a 46 kDa, respectively (Ceriani et al., 1983; Peterson et al, 1990). The 70 kDa glycoprotein (BA70) has been shown to be associated with the breast mucin by disulfide linkages, suggesting it to be a putative linker protein (Duwe et al., 1989) for the breast mucin. The 46 kDa glycoprotein (BA46) appears to be a member of a family of proteins having a domain with homology with the C1C2 domain of human coagulation factors V and VIII (Larocca et al, 1991). In this paper we will summarize the characteristics of the breast mucin and the 46 kDa antigen, present evidence on their epitopic heterogeneity, and suggest possible molecular strategy for selecting the most appropriate MoAbs for use in breast cancer diagnosis and therapy.


Breast Epithelial Cell Tandem Repeat Region Tandem Repeat Domain Malignant Breast Epithelial Cell Polymorphic Epithelial Mucin 
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  1. Burchell, J.M., Taylor-Papadimitriou, J., Boshell, M., Gendler, S.J., and Duhig, T., 1989, A short sequence, within the amino acid tandem repeat of a cancer-associated mucin, contains immunodominant epitopes, Int. J. Cancer 44: 691.PubMedCrossRefGoogle Scholar
  2. Ceriani, R.L., Thompson, K., Peterson, J.A., and Abraham, S., 1977, Surface differentiation antigens of human mammary epithelial cells carried on the human milk fat globule, Proc. Natl. Acad. Sci. USA 74: 582.PubMedCrossRefGoogle Scholar
  3. Ceriani, R.L., Sasaki, M., Sussman, H., Wara, W.M., and Blank, E.W., 1982, Circulating human mammary epithelial antigens in breast cancer, Proc. Natl. Acad. Sci. USA 79: 5420.PubMedCrossRefGoogle Scholar
  4. Ceriani, R.L., Peterson, J.A., Lee, J.Y., Moncada, R., and Blank, E.W., 1983, Characterization of cell surface antigens of human mammary epithelial cells with monoclonal antibodies prepared against human milk fat globule, Somatic. Cell Genet. 9: 415.PubMedCrossRefGoogle Scholar
  5. Ceriani, R.L., Peterson, J.A., and Blank, E.W., 1984, Variability in surface antigen expression of human breast epithelial cells cultured from normal breast, normal breast peripheral to breast carcinomas, and breast carcinomas, Cancer Res. 44: 3033.PubMedGoogle Scholar
  6. Ceriani, R.L. and Blank, E.W., 1988, Experimental therapy of human breast tumors with 1311-labeled monoclonal antibodies prepared against the human milk fat globule, Cancer Res. 48: 4664.PubMedGoogle Scholar
  7. Ceriani, R.L., Blank, E.W., Peterson, J.A., Battifora, H., and Singh, H., 1990, Immunotherapeutic preclinical evaluation of anti-human milk fat globule MoAbs Mc5 and BrE-1, Antibody Immunoconj. Radiopharm. 3: 181.Google Scholar
  8. Ceriani, R.L., Larocca, D., Peterson, J.A., Enloe, S., Amiya, R., and Blank, E.W., 1992, A novel serum assay for breast epithelial antigen using a fusion protein, Anal. Biochem. 201: 178.PubMedCrossRefGoogle Scholar
  9. Derbyshire, E.J. and Wawrzynczak, E.J., 1992, An anti-mucin immunotoxin BrE-3-ricin A-chain is potently and selectively toxic to human small-cell lung cancer, Int. J Cancer 52: 624.PubMedCrossRefGoogle Scholar
  10. Duwe, A.K. and Ceriani, R.L., 1989, Human milk fat globule membrane derived mucin is a disulfide-linked heteromer, Biochem. Biophys. Res Commun. 165: 1305.PubMedCrossRefGoogle Scholar
  11. Gendler, S.J., Lancaster, C.A., Taylor-Papadimitriou, J., Duhig, T., Peat, N., Burchell, J.M., Pemberton, L., Lalani, E.N., and Wilson, D., 1990, Molecular cloning and expression of human tumor-associated polymorphic epithelial mucin, J. Biol. Chem. 265: 15286.PubMedGoogle Scholar
  12. Hareuveni, M., Wreschner, D.H., Kieny, M.P., Dott, K., Gautier, C, Tomasetto, C, Keydar, I., Chambon, P., and Lathe, R., 1991, Vaccinia recombinants expressing secreted and transmembrane forms of breast cancer-associated epithelial tumour antigen (ETA), Vaccine 9: 618.PubMedCrossRefGoogle Scholar
  13. Hilkens, J. and Buijs, F., 1988, Biosynthesis of MAM-6, an epithelial sialomucin. Evidence for involvement of a rare proteolytic cleavage step in the endoplasmic reticulum, J. Biol Chem 263: 4215.PubMedGoogle Scholar
  14. Johnson, J.D., Edman, J.C., and Rutter, W.J., 1993, A receptor Tyrosine kinase found in breast carcinoma cells has an extracellular discoidin I-like domain, Proc. Natl. Acad. Sci. USA 90: 5677.PubMedCrossRefGoogle Scholar
  15. Kramer, E.L., DeNardo, S.J., Liebes, L., Kroger, L.A., Noz, M.E.G., Mizrachi, H., Salako, Q.A., Furmanski, P., Glenn, S.D., DeNardo, G.L., and Ceriani, R.L., 1993, Radioimmunolocalization of metastatic breast carcinoma using Indium-111-methyl benzyl DTPA BrE-3 monoclonal antibody: Phase 1 study, J. Nucl. Med. 34: 1067.PubMedGoogle Scholar
  16. Lan, M.S., Batra, S.K., Qi, W.N., Metzgar, R.S., and Hollingsworth, M.A., 1990, Cloning and sequencing of a human pancreatic tumor mucin cDNA, J. Biol. Chem. 265: 15294.PubMedGoogle Scholar
  17. Larocca, D., Peterson, J.A., Bistrain, A., Urrea, R., Kuniyoshi, J., and Ceriani, R.L., 1991, A 46 KDa human milk fat globule glycoprotein that is highly expressed in carcinoma cells has homology with human clotting factors V and VIII, Cancer Res. 51: 4994.PubMedGoogle Scholar
  18. Larocca, D., Peterson, J.A., and Ceriani, R.L., 1992, High level expression in E. coli of an alternate reading frame of pS2 mRNA that encodes a mimotope of human breast epithelial mucin tandem repeat, Hybridoma 11: 191.PubMedCrossRefGoogle Scholar
  19. Ligtenberg, M.J.L., Vos, H.L., Gennissen, A.M.C., and Hilkens, J., 1990, Episialin, a carcinoma-associated mucin, is generated by a polymorphic gene encoding splice variants with alternative amino termini, J. Biol. Chem. 265: 5573.PubMedGoogle Scholar
  20. Mather, I.H., Banghart, L.R., and Lane, W.S., 1993, The major fat-globule membrane proteins, bovine components 15/16 and guinea-pig GP 55, are homologous to MGF-E8, a murine glycoprotein containing epidermal growth factor-like and factor V/VHI-like sequences, Biochem. Mol. Biol Int. 29: 545.PubMedGoogle Scholar
  21. Nicolini, A., Colombini, C, Luciani, L., Carpi, A., and Giuliani, L., 1991, Evaluation of serum CA15-3 determination with CEA and TPA in the post-operative follow-up of breast cancer patients, Br. J. Cancer 64: 154.PubMedCrossRefGoogle Scholar
  22. Ortel, T., Devore-Carter, D., Quinn-Allen, M., and Kane, W.H., 1992, Deletion analysis of recombinant human factor V. Evidence for a phosphotidylserine binding site in the second C-type domain, J Biol. Chem. 267: 4189.PubMedGoogle Scholar
  23. Peat, N., Gendler, S.J., Lalani, N., Duhig, T., and Taylor-Papadimitriou, J., 1992, Tissue-specific expression of a human polymorphic epithelial mucin (MUC1) in transgenic mice, Cancer Res. 52: 1954.PubMedGoogle Scholar
  24. Peterson, J.A., Zava, D.T., Duwe, A.K., Blank, E.W., Battifora, H., and Ceriani, R.L., 1990, Biochemical and histological characterization of antigens preferentially expressed on the surface and cytoplasm of breast carcinoma cells identified by monoclonal antibodies against the human milk fat globule, Hybridoma 9: 221.PubMedCrossRefGoogle Scholar
  25. Peterson, J.A., Larocca, D., Walkup, G., Amiya, R., and Ceriani, R.L., 1991, Molecular analysis of epitope heterogeneity of the breast mucin, in: “Breast Epithelial Antigens: Molecular Biology to Clinical Applications,” R.L. Ceriani, ed., Plenum Publications, New York, p. 55.CrossRefGoogle Scholar
  26. Poole, S., Firtel, RA., and Lamar, E., 1981, Sequence and expression of the discoidin I gene family in dictyostelium discoideum, J. Mol. Biol. 153: 273.PubMedCrossRefGoogle Scholar
  27. Salinas, FA., Wee, K.H., and Ceriani, R.L., 1987, Significance of breast carcinoma-associated antigens as a monitor of tumor burden: characterization by monoclonal antibodies, Cancer Res. 47: 907.PubMedGoogle Scholar
  28. Stubbs, J.D., Lekutis, C, Singer, K.L., Bui, A., Yuzuki, D., Srinivasan, U., and Parry, G., 1990, cDNA cloning of a mouse mammary epithelial cell surface protein reveals the existence of epidermal growth factor-like domains linked to factor VIIMike sequences, Proc. Natl. Acad. Sci.USA 87: 8417.PubMedCrossRefGoogle Scholar
  29. Takagi, S., Hirata, T., Agata, K., Mochii, M., Eguchi, G., and Fujisawa, H., 1991, The A5 antigen, a candidate for the neuronal recognition molecule, has homologies to complement components and coagulation factors, Neuron 7: 295.PubMedCrossRefGoogle Scholar
  30. Wreschner, D.H., Hareuveni, M., Tsarfaty, I., Smorodinsky, N., Horev, J., Zaretsky, J., Kotkes, P., Weiss, M., Lathe, R., Dion, A., and Keydar, I., 1990, Human epithelial tumor antigen cDNA sequences, Eur. J. Biochem. 189: 463.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • Jerry A. Peterson
    • 1
  • Roberto L. Ceriani
    • 1
  1. 1.Cancer Research Fund of Contra CostaWalnut CreekUSA

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