Skip to main content
SpringerLink
Log in

Humoral immune response induced by the protein core of MUC1 mucin in pregnant and healthy women*

  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Serum levels of MUC1 and antibodies (Abs) against MUC1 (IgG and IgM-MUC1) were evaluated in healthy women related to pregnancy and lactation status. A total of 149 serum samples were obtained from: nulliparous, primiparous pregnant, multiparous pregnant that have lactated, multiparous pregnant without lactation, multiparous non-pregnant actual lactating, multiparous non-pregnant that have lactated and finally, multiparous non-pregnant women without lactation. In all assays, we included pre- and post-serum samples belonging to a breast cancer patient vaccinated with a MUC1 derived peptide. CASA test was employed to measure MUC1 while IgG- and IgM-MUC1 serum Abs were evaluated with an ELISA using a 100 mer peptide as catcher. In all groups, mean IgM levels were higher than IgG mean values; when samples were grouped in pregnants versus non-pregnants, a significant difference was detected with both Abs, being raised in non-pregnants. When samples were grouped in lactating versus non-lactating a significant difference was detected with IgG-MUC1, being raised in lactating women while no significant difference was found with IgM-MUC1. The evaluation of serum MUC1 levels confirmed previous results since a significant difference between pregnant versus non-pregnant groups was found while lactating versus non-lactating samples did not. Conclusions: (i) Increased MUC1 serum levels are apparently associated with pregnancy but not with lactation; (ii) MUC1 Abs are mainly associated with lactation and with non-pregnant status. These results may be considered a contribution on studies about protection against breast cancer induced by pregnancy and lactation.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Gendler SJ, Taylor-Papadimitriou J, Duhig T, Rothbar J, Burchell J: A highly immunogenic region of human polymorphic muc in expressed by carcinomas is made up of tandem repeats. J Biol Chem 263: 12820-12823, 1988

    Google Scholar 

  2. Finn OJ, Jerome KR, Henderson RA, Pecher G, Domenech N, Magarian-Blander J, Barratt-Boyes SM: MUC1 epithelial tumor mucin-based immunity and cancer vaccines. Immunol Rev 145: 61-89, 1995

    Google Scholar 

  3. Taylor Papadimitriou J, Stewart L, Burchell J, Beverly P: The polymorphic epithelial mucin as a target for immunotherapy. Ann NY Acad Sci 690: 69-79, 1993

    Google Scholar 

  4. Agrawal B, Krantz MJ, Reddish MA, Longenecker M: Cancer-associated MUC1 muc in inhibits human T-cell proliferation, which is reversible by IL-2. Nature Med 4: 43-49, 1998

    Google Scholar 

  5. Agrawal B, Krantz MJ, Parker J, Longenecker M: Expression of MUC1 muc in on activated human T cells: implications for a role of MUC1 in normal immune regulation. Cancer Res 58: 4079-4081, 1998

    Google Scholar 

  6. Brockhausen I, Romero PA, Herscovics A: Glycosiltransferase changes upon differentiation of CaCo-2 human colonic adenocarcinoma cells. Cancer Res 51: 3136, 1991

    Google Scholar 

  7. Linsley PS, Brown JP, Mangani JL, Horn D: Monoclonal antibodies reactive with mucin glycoproteins found in sera from breast cancer patients. Cancer Res 48: 2138-2148, 1998

    Google Scholar 

  8. Burchell J, Gendler S, Taylor-Papadimitriou J, Girling A, Lewis A, Millis R, Lamport D: Devlopment and characterization of breast cancer reactive monoclonal antibodies directed to the core protein of the human milk mucin. Cancer Res 47: 5476-5482, 1987

    Google Scholar 

  9. Devine P, McGuckin M, Quin R, Ward B: Serum CASA and CA15-3 in ovarian cancer: all MUC1 assays are not the same. Tumor Biol: 337-344, 1994

  10. Von Mensdorff-Pouilly S, Verstraeten AA, Kenemans P: Survival in early breast cancer patients is favorably influenced by a natural humoral immune response to polymorphic epithelial mucin (MUC1). J Clin Oncol 18: 574-583, 2000

    Google Scholar 

  11. Aplin JD, Hey NA, Graham RA: Human endometrial MUC1 carries keratan sulphate: characteristic glycoforms in the luminal epithelium at receptivity. Glycobiol 8: 269-276, 1998

    Google Scholar 

  12. Rye PD, Bell SC, Walker RA: Immunohistochemical expression of tumour associated glycoprotein and polymorphic epithelial mucin in the human endometrium during the menstrual cycle. J Reprod Fertil 97: 551-556, 1993

    Google Scholar 

  13. Hey NA, Graham RA, Seif MW, Aplin JD: The polymorphic epithelial mucin MUC1 in human endometrium is regulated with maximal expression in implantation phase. J Clin Endocrinol Metab 78: 337-342, 1994

    Google Scholar 

  14. Surveyor GA, Gendler S, Pemberton L, Das SK, Chakaborty L, Julian J, Pimental RA, Wegner CW, Day SK, Carson DD: Expression and steroid hormonal control of Muc1 in the mouse uterus. Endocrinology 136: 3639-3647, 1995

    Google Scholar 

  15. Wesseling J, van der Valk SW, Vos HL, Sonnenberg A, Hilkens J: Episial in (MUC1) overexpression inhibits integrin-mediated cell adhesion to extracellular matrix components. J Cell Biol 129: 255-265, 1995

    Google Scholar 

  16. Ligtenberg MJL, Buijs F, Vos HL, Hilkens J: Suppression of cellular aggregation by high levels of episialin. Cancer Res 52: 2318-2324, 1992

    Google Scholar 

  17. Agrawal B, Krantz MJ, Parker J, Longenecker M, Kenemans P, Bast RC, Yemeda CA, Price MR, Hilgers J: Mucins and mucin-like antigens as circulating tumor markers. In: Hilgers J, Zotter S (eds) Cancer Reviews, Vols 11, 12. Copenhagen: Munksgaard, 1989, pp 19-44

    Google Scholar 

  18. Kotera Y, Darrell Fontenot J, Pecher G, Metzgar RS, Finn O: Humoral immunity against a tandem repeat epitope of human mucin MUC1 in sera from breast, pancreatic and colon cancer patients. Cancer Res 54: 2856-2860, 1994

    Google Scholar 

  19. Richards ER, Devine P, Quin R, Darrell Fontenot J, Ward B, McGuckin M: Antibodies reactive with the protein core of MUC1 mucin are present in ovarian cancer patients and healthy women. Cancer Immunol Immunother 46: 245-250, 1998

    Google Scholar 

  20. Gourevitch MM, von Mensdorff-Pouilly S, Litvinov SV, Kenemans P, van Kamp GJ, Verstraeten AA, Hilgers J: Polymorphic epithelial mucin (MUC-1)-containing circulating immune complexes in carcinoma patients. Brit J Cancer 72: 934-938, 1995

    Google Scholar 

  21. Croce MV, Price MR, Segal-Eiras A: Expression of monoclonal antibody-defined antigens in fractions isolated from human breast carcinoma and patients' serum. Cancer Immunol Immunother 40: 132-137, 1995

    Google Scholar 

  22. Rughetti A, Turchi V, Apollonj Ghetti C, Scambia G, Panici PB, Rncucci G, Mancuso S, Frati L, Nuti M: Human B-cell immune response to the polymorphic epithelial mucin. Cancer Res 53: 2457-2459, 1993

    Google Scholar 

  23. Petrarca C, Casalino B, von Mensdorff-Pouilly S, Rughetti A, Rahimi H, Scambia G, Hilgers J, Frati L, Nuti M: Isolation of MUC1-primed B lymphocytes from tumour-draining lymph nodes by immunomagnetic beads. Cancer Immunol Immunother 47: 1999

  24. Croce MV, Isla-Larrain M, Price MR, Segal-Eiras A: Detection of circulating mammary mucin (MUC1) and MUC1 immune complexes (MUC1-CIC) in healthy women. Int J Biol Markers 16: 2001 (in press)

  25. Layton GT, Devine P, Warren JA: Monoclonal antibodies reactive with the breast carcinoma-associated muc in core protein repeat sequence peptide also recognise the ovarian carcinomaassociated sebaceous gland antigen (SGA). Tumor Biol 11: 274-286, 1990

    Google Scholar 

  26. Price MR, Pugh J, Hudecz F, O'sullivan C. Immunological and structural features of the protein core of human polymorphic epithelial mucin. Mol Immunol 27: 795-801, 1980

    Google Scholar 

  27. Von Mensdorff-Pouilly S, Gouretvich MM, Kenemans P: An enzyme-linked immunosorbent assay for the measurement of circulating antibodies to polymorphic epithelial mucin (MUC1). Tumor Biol 19: 186-195, 1989

    Google Scholar 

  28. Ravindranath MH, Bauer PM, Crowell Cornillez-Ty, García J, Morton DL: Quantitation of the density of cell surface carbohydrate antigens on cancer cells with a sensitive cellsuspension ELISA. J Immunol Meth 197: 51-67, 1996

    Google Scholar 

  29. Adluri S, Gilewski T, Zhang S, Ramnath V, Ragupathi G, Livingston P: Specificity analysis of sera from breast cancer patients vaccinated with MUC1-KLH plus QS-21. Br J Cancer 79: 1806-1812, 1999

    Google Scholar 

  30. Miles DW, Taylor-Papadimitriou J: Therapeutic aspects of polymorphic epithelial mucin in adenocarcinoma. Pharmacol Ther 82: 97-106, 1999

    Google Scholar 

  31. Gilewski T, Adluri R, Ragupathi G, Zhang S, Yao T-J, Panageas K, Moynahan M, Houghton AN, Norton L, Livingston PO: Vaccination of high-risk breast cancer patients with mucin-1 (MUC1)-keyhole limpet hemocyanin conjugate plus QS-21. J Clin Cancer Res 60: 1693-1701, 2000

    Google Scholar 

  32. Zhang H, Zhang S, Cheung NK, Ragupathi G, Livingston PO: Antibodies can eradicate cancer micrometastasis. Cancer Res 58: 2844-2849, 1998

    Google Scholar 

  33. Ragupathi G, Howard l, Cappello S, Rao Koganty R, Qiu D, Longenecker BM, Reddish MA, Lloyd K, Livingston P: Vaccines prepared with sialyl-Tn and sialyl-Tn trimers using the 4-(4-maleimidomethyl)cyclohexane-1-carboxyl hydrazide linker group result in optimal antibody titers against ovine submaxillary mucin and sialyl-Tn-positive tumor cells. Cancer Immunol Immunother 48: 1-8, 1999

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Comisión de Investigaciones Científicas de la Provincia de Buenos Aires (CICPBA), Argentina

    María V. Croce

  2. Centro de Investigaciones Inmunológicas Básicas y Aplicadas (CINIBA), Facultad de Ciencias Médicas, UNLP, Argentina

    Marina T. Isla-Larrain & Adriana Capafons

  3. The Cancer Research Laboratory, School of Pharmaceutical Sciences, Nottingham, UK

    Mike R. Price

  4. Research Worker Career of the Consejo Nacional de Investigaciones Científicas y Técnicas, Argentina

    Amada Segal-Eiras

Authors
  1. María V. Croce
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marina T. Isla-Larrain
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Adriana Capafons
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mike R. Price
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Amada Segal-Eiras
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Croce, M.V., Isla-Larrain, M.T., Capafons, A. et al. Humoral immune response induced by the protein core of MUC1 mucin in pregnant and healthy women*. Breast Cancer Res Treat 69, 1–11 (2001). https://doi.org/10.1023/A:1012220902991

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1012220902991

Search

Navigation