Abstract
The immunophenotype of HT29 human colon cancer cells implanted into severe combined immunodeficient mice was assessed in primary tumours and their metastases in the lungs using an indirect immunohistochemical method. After primary tumours were surgically removed, the metastases were given time to develop, thus paralleling the clinical situation. While vimentin was negative in both primary and secondary tumours, E-cadherin was present as membrane-bound labelling in the primary tumours only. Whereas the markers p53, MIB1, PCNA and CEA were consistently positive in both primary and metastatic tumours, CD44 variant 6 and CA125 were negative in metastases but positive in the primary tumours. There was a significant increase in the percentage of cells labelled for p53 in the primary tumours compared with the metastases. For the proliferation markers, there was no significant difference in labelling between primary tumours and metastases for MIB1. Of the cytokeratins examined, CK 20 gave the strongest and most consistent reaction in both primary and secondary tumours. The results indicate that, for certain immunohistochemical markers, results are the same in both primary tumours and metastases. Hence, in these cases, antigens that are expressed on the primary tumour as well as on the metastases can serve as target molecules for immunologically based forms of treatment of metastases.
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Bresalier, R.S., Raper, S.E., Hujanen, E.S. & Kim, Y.S. (1987) A new animal model for human colon cancer metastasis. J. Cancer39, 625-30.
Cooper, D., Schermer, A., & Sun, T.-T. (1985) Classification of human epithelia and their neoplasms using monoclonal antibodies to keratins: strategies, applications, and limitations. Lab. Invest.52, 243-56.
Dietel, M., Arps, H., Klapdor, R., Muller-Hagen, S., Sieck, M. & Hoffmann, L. (1986) Antigen detection by the monoclonal antibodies CA 19–9 and CA 125 in normal and tumour tissue and patients' sera. J. Cancer Res. Clin. Oncol.111, 257-65.
Fantini, J., Rognoni, J., Culouscou, J., Pommier, G., Marvaldi, J. & Tirard, A. (1990) Induction of polarized apical expression and vectorial release of carcinoembryonic antigen (CEA) during the process of differentiation of HT29-D4 cells. J. Cell. Physiol.141, 126-34.
Friedrichs, K., Franke, F., Lisboa, B., Kugler, G., Gille, I., Terpe, H.J., Holzel, F., Maass, H. & Gunthert, U. (1995) CD44 isoforms correlate with cellular differentiation but not with prognosis in human breast cancer. Cancer Res.55, 5424-33.
Goddard, M.J., Wilson, B. & Grant, J.W. (1991) Comparison of commercially available cytokeratin antibodies of normal and neoplastic adult epithelial and non-epithelial tissues. J. Clin. Pathol.44, 660-3.
Hamana, T., Kawai, K., Serizawa, A., Tsutumi, Y. & Wantanabe, K. (1994) Immunohistochemical demonstration of p53 protein in colorectal adenomas and adenocarcinomas. Reliable application of the heat-induced antigen retrieval method to formalin-fixed, paraffin-embedded material. Pathol. Int.44, 765-70.
Hart, I.R., Goode, N.R. & Wilson, R.E. (1989) Molecular aspects of the metastatic cascade. Biochim. Biophys. Acta998, 65-84.
Horstetter, R.B., Campbell, D.E., Kefung, C., Kerckhoff, S., Cleary, K.R., Ullrich, S., Thomas, P. & Jessup, M. (1990) Carcinoembryonic antigen enhances metastatic potential of human colorectal carcinoma. Arch. Surg.125, 300-4.
Hsu, S., Raine, L. & Fanger, H. (1981) Use of avidinbiotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabelled antibody (PAP) procedures. J. Histochem. Cytochem.29, 577-80.
Knox, R.J. & Connors, T.A. (1995) Antibody-directed enzyme prodrug therapy. Clin. Immunother.3, 136-53.
Lane, E.B. & Alexander, C.M. (1990) Use of keratin antibodies in tumour diagnosis. Cancer Biol.1, 165-79.
Leake, J., Woolas, R.P., Daniel, J., Oram, D.H. & Brown, C.L. (1994) Immunocytochemical and serological expression of CA 125: a clinicopathological study of 40 malignant ovarian epithelial tumours. Histopathology24, 57-64.
Maehara, Y., Okuyama, T., Kakeji, Y., Endo, K., Yamamoto, M. & Sugimachi, K. (1995) A tumour-associated cell-surface glycoprotein accompanying p53 overexpression and higher growth potential for gastric cancer. Br. J. Cancer71, 999-1002.
Maruyama, K., Tanaka, T., Bab, S., Nakamura, S., Endo, Y. & Sugimura, H. (1996) p53 accumulation in colorectal cancer with hepatic metastases. Jpn J. Cancer Res.87, 368-76.
Mitchell, B.S., Schumacher, U. & Kaiserling, E. (1994) Are tumours innervated? Immunohistological investigations using antibodies against the neuronal marker protein gene product 9.5 (PGP 9.5) in benign, malignant and experimental tumours. Tumor Biol.15, 269-74.
Mitchell, B.S., Whitehouse, A., Prehm, P., Delpech, B. & Schumacher, U. (1996) CD44 exon variant 6 epitope and hyaluronate synthase are expressed on HT29 human colorectal carcinoma cells in a SCID mouse model of metastasis formation. Clin. Exp. Metas.14, 107-14.
Moll, R., Franke, W.W. & Schiller, D.L. (1982) The catalog of human cytokeratins: pattern of expression in normal epithelia, tumors and cultured cells. Cell31, 11-24.
Moll, R., Lowe, A., Laufer, J. & Franke, W.W. (1992) Cytokeratin 20 in human carcinomas. Am. J. Pathol.140, 427-47.
Nikiforov, M.A., Hagen, K., Ossovskaya, V.S., Connor, T.M.F., Lowe, S.W., Deichman, G.I. & Gudkov, A.V. (1996) p53 modulation of anchorage-independent growth and experimental metastasis. Oncogene13, 1709-19.
Ponta, H., Sleemann, J. & Herrlich, P. (1994) Tumor metastasis formation: cell-surface proteins confer metastasis-promoting or-suppressing properties. Biochim. Biophys. Acta1198, 1-10.
Radinsky, R. (1993) Paracrine growth regulation of human colon carcinoma organ-specific metastasis. Cancer Metas. Rev.12, 345-61.
Schumacher, U., Adam, E., Flavell, D.J., Boehm, D., Brooks, S.A. & Leathem, A.J. (1994a) Glycosylation of the human colon cancer cell line HT-29 detected by Helix pomatia agglutinin and other lectins in culture, in primary tumours and in metastases in SCID mice. Clin. Exp. Metas.12, 398-404.
Schumacher, U., Higgs, D., Loizidou, M., Pickering, R., Leathem, A., & Taylor, I. (1994b) Helix pomatia agglutinin binding is a useful prognostic indicator in colorectal carcinoma. Cancer74, 3104-7.
Schumacher, U., Adam, E., Brooks, S. & Leathem, A. (1995) Clinically relevant animal models for metastasis research using severe combined immunodeficient (SCID) mice and human cancer cell lines. Proc. R.M.S.30, 133.
Speiser, P., Wanner, C., Breitnecker, G., Kohlberger, P. & Kainz, C. (1995) CD44 is not involved in the metastatic spread of ovarian cancer in vivo. Anticancer Res.15, 2767-9.
Sun, X.F., Cartensen, J.M., Stal, O., Zhang, H. & Nordenskold, B. (1994) C-erb-2 and p53 oncoproteins in primary colorectal adenocarcinomas and their lymph node metastases. Diagnostic Oncol4, 161-4.
Sun, W.F., Cartensen, K.M., Stal, O., Zhang, H. & Nordenskjold, B. (1996) Proliferating cell nuclear antigen (PCNA) in relation to ras, c-erb-2, p53, clinicopathological variables and prognosis in colorectal adenocarcinoma. Int. J. Cancer69, 5-8.
Taghian, A. & Huang, P. (1994) The nude and SCID mice as a tumor model in experimental cancer biology. Cancer J.8, 59-61.
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Mitchell, B., Horny, HP. & Schumacher, U. Immunophenotyping of human HT29 colon cancer cell primary tumours and their metastases in severe combined immunodeficient mice. J Mol Hist 29, 393–399 (1997). https://doi.org/10.1023/A:1026490901926
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DOI: https://doi.org/10.1023/A:1026490901926