Abstract
The human cell-surface antigen epithelial glycoprotein-2 recognized by the monoclonal antibody MOC-31 is an epithelial tumour-associated glycoprotein expressed in non-squamous carcinomas. MOC-31 immunoreactivity was investigated in human breast, colon, ovarian and lung cancer cell lines, grown either in vitro or in severe combined immunodeficient (SCID) mice as solid tumours and/or metastases. Three of four small-cell lung cancer cell lines (NCI-H69, OH3 and SW2) and three of four ovarian cancer cell lines (SoTü 1, 3 and 4) expressed epithelial glycoprotein-2. In contrast, all three breast (MCF-7, BT20, T47D) and all three colon (HT29, CACO2, SW480) cancer cell lines strongly reacted with monoclonal antibody MOC-31. A notable difference in MOC-31 immunoreactivity was observed in spontaneously formed lung metastases of HT29 colon cancer cells. Whereas larger metastases (> 30 cells) re acted with a similar staining pattern to the primary tumour, smaller metastases did not. These findings indicate that differentiation processes during the epithelial–mesenchymal transition occur in metastases, which lead to a transient loss of epithelial glycoprotein-2 expression during the migratory and early post- migratory period. This loss of antigen expression indicates that the process of metastases formation is a regulatory event, and this transient loss of antigen expression might represent a potential obstacle to antibody-based therapy in the setting of minimal residual disease.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Basak, S., Speicher, D., Eck, S., Wunner, W., Maul, G., Simmons, M.S. & Herlyn, D. (1998) Colorectal carcinoma invasion inhibition by CO17-1A/GA733 antigen and its murine homologue. J. Natl. Cancer Inst. 90, 691–7.
Birchmeier, C., Birchmeier, W. & Brand-Saberi, B. (1996) Epithelial-mesenchymal transitions in cancer progression. Acta Anat. 156, 217–26.
Bumol, T.F., Marder, P., Deherdt, S.V., Borowitz, M. J. & Apelgren, L.D. (1988a) Characterization of the human tumour and normal tissue reactivity of the KS1/4 monoclonal antibody. Hybridoma 7, 407–15.
Bumol, T.F., Baker, A.L., Andrews, E.L., Deherdt, S.V., Briggs, S.L., Spearman, M. & Apelgren, L.D. (1988b) KS1/4-DAVLB, a monoclonal antibody-vinca alcaloid conjugate for site-directed therapy of epithelial malignancies. Targeted Diagn. Ther. 1, 55–79.
De Leij, L., Poppema, S., Nulend, K., Ter Haar, J.G., Schwander, E. & The, T.H. (1984) Immunoperoxidase staining on frozen tissue sections as a first screening assay in the preparation of monoclonal antibodies directed against small cell carcinoma of the lung. Eur. J. Cancer Clin. Oncol. 20, 123–8.
De Leij, L., Postmus, P.E., Poppema, S., Elema, J.D. & The, T.H. (1986) The use of monoclonal antibodies for the pathological diagnosis of lung cancer. In Lung Cancer: Basic and Clinical Aspects, 1st edn (edited by H.H. Hansen), pp. 31–48. Boston: Martinus Nyhoff Publishers.
De Leij, L., Helrich, W., Stein, R. & Mattes, M. J. (1994) SCLC-cluster-2 antibodies detect the pancarcinoma/ epithelial glycoprotein EGP-2. Int. J. Cancer (Suppl.) 8, 60–3.
Edwards, D.P., Grzyb, K.T., Dressler, L.G., Mansel, R.E., Zara, D.T., Sledge, G.W. & Mcguire, W.L. (1986) Monoclonal antibody identification and characterization of a Mr 34,000 human epithelium-specific surface glycoprotein associated with human breast cancer. Cancer Res. 46, 1306–17.
GÖttlinger, H.G., Funke, I., Johnson, J.P., Gokel, J.M. & RiethmÜller, G. (1986) The epithelial cell surface antigen 17-1A, a target for antibody-mediated tumour therapy: its biochemical nature, tissue distribution and recognition by different monoclonal antibodies. Int. J. Cancer 38, 47–53.
Herlyn, M., Steplewski, Z., Herlyn, D. & Koprowski, H. (1979) Colorectal carcinoma-specific antigen: detection by means of monoclonal antibodies. Proc. Natl. Acad. Sci. USA 76, 1438–42.
Koprowski, H., Herlyn, D., Lubeck, M., Defrietas, E. & Sears, H.F. (1984) Human anti-idiotype antibodies in cancer patients: is the modulation of the immune response beneficial for the patient? Proc. Natl. Acad. Sci. USA 81, 216–19.
Moldofsky, P.J., Powe, J., Mulhern, C.B., Sears, H.F., Hammond, N.P., Gatenby, R.A., Steplewski, Z. & Koprowski, H. (1983) Imaging with radiolabelled F(ab9)2 fragments of monoclonal antibody in patients with gastrointestinal carcinoma. Radiology 149, 549–55.
Momburg, F., Moldenhauer, G., Hammerling, G.J. & Moller, P. (1987) Immunohistochemical study of the expression of a Mr 34,000 human epithelium-specific surface glycoprotein in normal and malignant tissues. Cancer Res. 47, 2883–91.
Perez, M.S. & Walker, L.E. (1989) Isolation and characterization of a cDNA encoding the KS1/4 epithelial carcinoma marker. J. Immunol., 142, 3662–7.
Schumacher, U. & Adam, E. (1998) Immunohistochemical detection of the MUC1 gene product in human cancers grown in scid mice. J. Histochem. Cytochem. 45, 1–8.
Schumacher, U., Mohamed, M. & Mitchell, B.S. (1996) Differential expression of carbohydrate residues in human breast and colon cancer cell lines grown in vitro and in vivo in SCID mice. Cancer J. 9, 247–54.
Sears, H.F., Mattis, J., Herlyn, D., HÄ yry, P., Atkinson, B., Ernst, C., Steplewski, Z. & Koprowski, H. (1982) Phase-I clinical trial of monoclonal antibody treatment of gastrointestinal tumours. Lancet 1, 762–5.
Sears, H.F., Herlyn, D., Steplewski, Z. & Koprowski, H. (1984) Effects of monoclonal antibody immunotherapy on patients with gastrointestinal adenocarcinoma. J. Biol. Resp. Modif. 3, 138–50.
Sears, H.F., Herlyn, D., Steplewski, Z. & Koprowski, H. (1985) Phase II clinical trial of a murine monoclonal antibody cytotoxic for gastrointestinal adenocarcinoma. Cancer Res. 45, 5910–13.
Shen, J.-W., Atkinson, B., Koprowski, H. & Sears, H.F. (1984) Binding of murine immunoglobulin to human tissues after immunotherapy with anticolorectal carcinoma monoclonal antibody. Int. J. Cancer 33, 465–8.
Souhami, R.L., Beverley, P.C.L. & Bobrow, L.G. (1988) Proceedings of the First International Workshop on Small-Cell Lung-Cancer Antigens. Lung Cancer 4, 1–114.
Spearman, M.E., Goodwin, R.M., Apelgren, L.D. & Bumol, T.F. (1987) Disposition of the monoclonal antibody-vinca alkaloid conjugate KS1/4-DAVLB (LY256787) and free 4-desacetylvinblastine in tumour bearing nude mice. J. Pharmacol. Exp. Ther. 241, 695–703.
Spurr, N.K., Durbin, H., Sheer, D., Parkar, M., Bobrow, M. & Bodmer, W.F. (1986) Characterization and chromosomal assignment of a human cell surface antigen defined by monoclonal antibody AUA1. Int. J. Cancer 38, 631–6.
Stahel, R.A., Gilks, W.R., Lehmann, H.P. & Schenker, T. (1994) International workshop on lung tumour and differentiation antigens: overview of the results of the central data analysis. Int. J. Cancer (Suppl.) 8, 6–26.
Szala, S., Froehlich, M., Scollon, M., Kasai, Y., Steplewski, Z., Koprowski, H. & Linnebach, A. J. (1990) Molecular cloning of cDNA for the carcinoma-associated antigen GA733-2. Proc. Nat. Acad. Sci. USA 87, 3542–6.
Varki, N.M., Reisfeld, R.A. & Walker, L.E. (1984) Antigens associated with a human lung adenocarcinoma defined by monoclonal antibodies. Cancer Res. 44, 681–7.
Zimmermann, S., Wels, W., Froesch, B.A., Gerstmayer, B., Stahel, R. A. & Zangemeister-Wittke, U. (1997) A novel immunotoxin recognising the epithelial glycoprotein-2 has potent antitumoural activity on chemotherapy-resistant lung cancer. Cancer Immunol. Immunother. 44, 1–9.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Jojović, M., Adam, E., Zangemeister-Wittke, U. et al. Epithelial Glycoprotein-2 Expression is Subject to Regulatory Processes in Epithelial–mesenchymal Transitions During Metastases: an Investigation of Human Cancers Transplanted into Severe Combined Immunodeficient Mice. Histochem J 30, 723–729 (1998). https://doi.org/10.1023/A:1003486630314
Issue Date:
DOI: https://doi.org/10.1023/A:1003486630314