Abstract
Objective
Because epidemiologic data indicate a reduction in ovarian cancer risk with increased parity, the occurrence of maternal immunization against ovarian tumor-associated antigens during pregnancy was investigated.
Methods
Sera were obtained from nulligravid and multiparous women and from men. Cellular proteins were isolated from four ovarian tumor cell lines as well as from normal ovaries. These proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and the presence of cellular proteins reactive with each individual’s serum was assessed by Western immunoblot. Tumor-reactive antibodies from two multiparous women were used to prepare immunoaffinity columns for the isolation of reactive proteins from ovarian tumor cells. These immunoaffinity-purified antigens were transferred electrophoretically to nitrocellulose membranes, stained with Ponceau S, and identified by amino acid sequencing.
Results
Western immunoblot analysis of the cellular proteins from four established ovarian tumor cell lines using sera from multiparous women as the primary antibody indicated that these samples recognized multiple bands on ovarian tumors, ranging from 30 to 150 kD. Two commonly recognized proteins were isolated and subjected to microsequencing, which identified the 56-kD band protein as elongation factor- 1α and the 38-kD protein as nucleophosmin/B23 protein. Both of these proteins play integral roles in cell growth.
Conclusion
These findings suggest that certain antigens expressed by the fetus immunize women during pregnancy. This immune response may protect these women from the subsequent development of cancer.
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References
Patel AR, Obrams GI. Epidemiology of ovarian cancer. Cancer Epidemiol Biomarkers Prev 1993;2:79–83.
Perez RP, Godwin AK, Hamilton TC, Ozols RF. Ovarian cancer biology [Review]. Semin Oncol 1991;18:186–204.
Janerich DT. The fetal antigen hypothesis for breast cancer, revisited. Med Hypotheses 1994;43:105–10.
Polednak AP, Janerich DT. Characteristics of first pregnancy in relation to early breast cancer. J Reprod Med 1983;28:314–8.
Janerich DT. The influence of pregnancy on breast cancer risk. Med Hypotheses 1980;6:1149–55.
Agrawal B, Reddish MA, Krantz MJ, Longenecker BM. Does pregnancy immunize against breast cancer? Cancer Res 1995;55:2257–61.
Burchell J, Gendler S, Taylor-Papadimitriou J, et al. Development and characterization of breast cancer reactive monoclonal antibodies directed to the core protein of the human milk mucin. Cancer Res 1987;47:5476–82.
Taylor DD, Doellgast GJ. Quantitation of peroxidase-antibody binding to membrane fragments using column chromatography. Anal Biochem 1979;98:53–9.
Taylor VD, Homesley HD, Doellgast GJ. “Membrane-associated” immunoglobulins in cyst and ascites fluids of ovarian cancer patients. Am J Reprod Immunol 1983;3:7–11.
Taylor DD, Homesley HD, Doellgast GJ. Identification of antigenic components recognized by “membrane bound” antibodies from ovarian cancer patients. Am J Reprod Immunol 1984;6:179–84.
Old LJ. Cancer immunology): The search for specificity - G. H. A. Clowes Memorial Lecture. Cancer Res 1981;41:361–75.
Taylor DD, Black PH. Shedding of plasma membrane fragments: Neoplastic and developmental importance. Dev Biol 1986;3:33–57.
Hellstrom KE, Hellstrom I. Principles of tumor immunity: Tumor antigens. In: DeVita VT, Hellman S, Rosenberg SA. eds. Biologic therapy of cancer. New York: Lippincott, 1991:35–52.
Vlock DR, Scalise D, Schwartz DR, et al. Incidence of serum antibody reactivity to autologous head and neck cancer cell lines and augmentation of antibody reactivity following acid dissociation and ultrafiltration. Cancer Res 1989;49:1361–5.
Owens K, Gercel-Taylor C, Taylor DD, Day TG, Doering DL. Isolation and characterization of an ovarian carcinoma cell line as a model for drug resistance. Proc Am Assoc Cancer Res 1993;34:26.
Testa JR, Getts LA, Salazar H, et al. Spontaneous transformation of rat ovarian surface epithelial cells results in well to poorly differentiated tumors with a parallel range of cytogenetic complexity. Cancer Res 1994;54:2778–84.
Brown R, Clugston C, Burns P, et al. Increased accumulation of p53 protein in cisplatin-resistant ovarian cell lines. Int J Cancer 1993;5:678–84.
Laemmli UK. Cleavage of structural proteins during the assembly of the head of the bacteriophage T4. Nature 1970;227:680–5.
Lui M, Tempst P, Erdjument-Bromage H. Methodical analysis of protein-nitrocellulose-m interactions to design a refined digestion protocol. Anal Biochem 1996;241:156–66.
Forsman LM, Jouppila PI, Andersson LC. Sera from multiparous women contain antibodies mediating cytotoxicity against breast carcinoma cells. Scand J Immunol 1984;19:135–9.
Gendîer S, Taylor-Papadimitriou J, Duhig T, Rothbard J, Burchell J. A highly immunogenic region of a human polymorphic epithelial mucin expressed by carcinomas is made up of tandem repeats. J Biol Chem 1988;263:12820–3.
Heller R, Fisher R, Nash A, Knapp J. Lack of relationship between parity and level of carcinoembryonic antigen in women with breast cancer. Anticancer Res 1990;10:1755–7.
Ioannides CG, Fisk B, Jerome KR, Irimura T, Wharton JT, Finn OJ. Cytotoxic T cells from ovarian malignant tumors can recognize polymorphic epithelial mucin core peptides. J Immunol 1993;151:3693–703.
Jacobson HI, Thompson WD, Janerich DT. Multiple births and maternal risk of breast cancer. Am J Epidemiol 1989;129:865–73.
Tatsuka M, Mitsui H, Wada M, Nagata A, Nojima H, Okayama H. Elongation factor-1 alpha gene determines susceptibility to transformation. Nature 1992;359:333–6.
Grant A, Flomen R, Tizard M, Grant D. Differential screening of a human pancreatic adenocarcinoma lambda gt11 expression library has identified increased transcription of elongation factor EF-1 alpha in tumour cells. Int J Cancer 1992;50:740–5.
Sonenberg N. Translational factors as effectors of cell growth and tumorigenesis. Curr Opin Cell Biol 1993;5:955–60.
Sorokine I, Ben-Mahrez K, Bracone A, et al. Presence of circulating anti-c-myb oncogene product in human sera. Int J Cancer 1991;47:665–9.
Kotera Y, Fontenot D, Pecher G, Metzgar RS, Finn OJ. Humoral immunity against a tandem repeat epitope of human mucin MUC-1 in sera from breast, pancreatic, and colon cancer patients. Cancer Res 1994;54:2856–60.
Winter SF, Minna JD, Johnson BE, Takahashi T, Gazdar AF, Carbone DP. Development of antibodies against p53 in lung cancer patients appears to be dependent on the type of p53 mutation. Cancer Res 1992;52:4168–74.
Mayordomo JI, Loftus DJ, Sakamoto H, et al. Therapy of murine tumors with p53 wild-type mutant sequence peptide-based vaccines. J Exp Med 1996;183:1357–65.
Nozawa Y, Van Beizen N, Van der Made A, Dinjens W, Bosman F. Expression of nucleophosmin/B23 in normal and neoplastic colorectal mucosa. J Pathol 1996;178:48–52.
Herrera J, Savkur R, Olson M. The ribonuclease activity of nucleolar protein B23. Nucleic Acids Res 1995;23:3974–9.
Finch R, Chan P. Studies of actinomycin D induced B23-translocation in P388D1 cells implanted in DBA/2 mice. Oncology 1992;49:223–6.
Wang D, Umekawa H, Olson M. Expression and subcellular locations of two forms of nucleolar protein B23 in rat tissues and cells. Cell Mol Biol Res 1993;39:33–42.
Imai H, Kiyosawa K, Chan EK, Tan EM. Autoantibodies in viral hepatitis-related hepatocellular carcinoma. Intervirology 1993;35:75–85.
Ochs RL, Stein TW, Chan EK, Ruutu M, Tan EM. CDNA cloning and characterization of a novel nucleolar protein. Mol Biol Cell 1996;7:1015–24.
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This work was supported by a grant (95-12) from the Alliant Community Trust Fund of the Alliant Health Systems.
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Shields, L.B.E., Gerçel-Taylor, Ç., Yashar, C.M. et al. Induction of Immune Responses to Ovarian Tumor Antigens by Multiparity. Reprod. Sci. 4, 298–304 (1997). https://doi.org/10.1177/107155769700400606
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DOI: https://doi.org/10.1177/107155769700400606