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Studies of mammary carcinoma metastasis in a mouse model system. I: Derivation and characterization of cells with different metastatic properties during tumour progression in vivo

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Abstract

The biological and metastatic properties of cells from a murine mammary adenocarcinoma, MTI, were studied during serial transplantation in syngeneic hosts. Over 35 generations the tumour progressed from a well-differentiated, poorly metastatic neoplasm to an anaplastic highly metastatic state. At early passages the tumour yielded uniform cultures of cuboidal epithelial cells, at passage 17 both epithelioid and spindle type cells were present, and by passage 30 only spindle type cells were obtained. Epithelioid cell lines and clones when injected intravenously into syngeneic hosts produced lung colonies only, whereas spindle cell lines were capable of extensive extrapulmonary colonisation. Similar patterns of dissemination and growth were seen in spontaneous metastasis assays. In spite of the marked phenotypic differences in these ‘subpopulations’, their comparable ultrastructural features, oestrogen receptor levels, expression of MMTV antigens, DNA content and lectin binding profiles suggested a common cell lineage. It is proposed that these cell lines will be of use in the determination of tumour and host factors influencing tumour progression and the evolution of metastatic potential.

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References

  1. Anderson, J. C., Fugmann, R. A., Stolfi, R. L., and Martin, D. S., 1974, Metastatic incidence of a spontaneous murine mammary adenocarcinoma. Cancer Research, 34 1916–1920.

    Google Scholar 

  2. Begg, A. C., 1971, Kinetic and histological changes of a serially transplanted mouse tumour. Cell and Tissue Kinetics, 4 401–411.

    Google Scholar 

  3. Bennett, D. C., Peachey, L. A., Durbin, H., and Rudland, P. S., 1978, A possible mammary stem cell line. Cell, 15 283–288.

    Google Scholar 

  4. Chang, S. E., Keen, J., Lane, E. B., and Taylor-Papadimitriou, J., 1982, Establishment and characterisation of SV-40 transformed human breast epithelial cell lines. Cancer Research, 42 2040–53.

    Google Scholar 

  5. Chow, D. A., and Greenberg, A. H., 1980, The generation of tumour heterogeneity in vivo. International Journal of Cancer, 25 261–265.

    Google Scholar 

  6. Dexter, D. L., Kowalski, H. M., Blazar, B. A., Fligiel, Z., Vogel, R., and Heppner, G. H., 1978, Heterogeneity of tumour cells from a single mouse mammary tumour. Cancer Research, 38 3174–3181.

    Google Scholar 

  7. Dulbecco, R., Henahan, M., Bowman, M., Okada, S., Battifora, H., and Ungar, M., 1981, Generation of fibroblast-like cells from cloned epithelial mammary cells in vitro; a possible new cell type. Proceedings of The National Academy of Science, U.S.A., 78 2345–2349.

    Google Scholar 

  8. Dunn, T., 1959, Morphology of mammary tumors in mice, Physiopathology of Cancer. Second edition, edited by F. Momburger and N. H. Fishman (New York: Paul B. Hoeber, Inc.) pp. 38–84.

    Google Scholar 

  9. Eccles, S., 1972, Host factors in metastasis In Tumor Progression and Markers. Proceedings of the VIth meeting of the European Association for Cancer Research (Amsterdam: Kugler), pp. 183–196.

    Google Scholar 

  10. Eccles, S., 1983, Invasion and metastasis: experimental systems. Proceeding of Symposium on Recent Advances in Malignancy. Journal of Pathology, 140 (in the press).

  11. Falk, P., 1982, Differences in vascular pattern between the spontaneous and the transplanted C3H mouse mammary carcinoma. European Journal of Cancer and Clinical Oncology, 18, 155–165.

    Google Scholar 

  12. Fidler, I. J., and Hart, I.R., 1981, Biological and experimental consequences of the zonal composition of solid tumours. Cancer Research, 41 3266–3267.

    Google Scholar 

  13. Foulds, L., 1949, Mammary tumours in hybrid mice: growth and progression of spontaneous tumours. British Journal of Cancer, 345–375.

  14. Hager, J. C., Fligiel, S., Stanley, W., Richardson, A. M., and Heppner, G. H., 1981, Characterisation of a variant producing tumor cell line from a heterogeneous strain BALB/cfC3H mouse mammary tumor. Cancer Research, 41, 1293–1300.

    Google Scholar 

  15. Hiraki, K., Irino, S., Miyoshi, I., and Harada, H., 1965, In vivo and in vitro studies of sarcomatous transformation of mammary carcinoma in AKR mice. Gann, 56, 403–410.

    Google Scholar 

  16. Kim, U., 1979, Factors influencing metastasis of breast cancer. Breast Cancer Volume 3, edited by W. L. McGuire (Plenum), pp. 1–49.

  17. Kuhn, H., 1981, A simple method for the preparation of cell cultures for ultrastructural investigation. Journal of Histology and Cytology, 29, 84–86.

    Google Scholar 

  18. Kuzumaki, N., More, I. A. R., Cochran, A. J., and Klein, G., 1980, Thirteen new mammary tumor cell lines from different mouse strains. European Journal of Cancer, 16, 1181–1192.

    Google Scholar 

  19. Lane, E. B., 1982, Monoclonal antibodies provide specific intracellular markers for the study of epithelial tonofilament organisation. Cold Spring Harbor Symposium on Quantitative Biology, 46, 387–482.

    Google Scholar 

  20. Lazarides, I., 1980, Intermediate filaments as mechanical integrators of cellular space. Nature, 283, 249–256.

    Google Scholar 

  21. Lee, C., Lapin, V., Oyasu, R., Battifora, H., 1981, Effect of Ovarlectomy on serially transplanted rat mammary tumors induced by 7,12-dimethylbenz(a)anthracene. European Journal of Cancer and Clinical Oncology, 17, 801–808.

    Google Scholar 

  22. Liotta, L. A., Kleinerman, J., and Saidel, G., 1976, The significance of haematogenous tumour cell clumps in the metastatic process. Cancer Research, 36, 889–894.

    Google Scholar 

  23. Mackenzie, D. H., 1957, Reticulin patterns in the diagnosis of carcinomas and sarcomas. British Journal of Cancer, 12, 14–19.

    Google Scholar 

  24. McGrath, G. M., 1971, Replication of mammary tumor virus in tumor cell cultures: dependence on hormone induced cellular organisation. Journal of the National Cancer Institute, 47, 455.

    Google Scholar 

  25. Malejka-Giganti, D., Potter, A. H., and Rydell, R. E., 1980, A fibrosarcoma component in culture of a chemically induced rat mammary adenocarcinoma. Laboratory Investigations, 42, 627–35.

    Google Scholar 

  26. Medina, D., 1975, Tumour progression. Cancer, a comprehensive treatise. Volume 3, edited by F. F. Becker (New York: Plenum), pp. 99–119.

    Google Scholar 

  27. Miller, B. E., Miller, F. R., Leith, J., and Heppner, G. H., 1980, Growth interaction in vivo between tumour subpopulations derived from a single mouse mammary tumor. Cancer Research, 40, 3977–3981.

    Google Scholar 

  28. Moore, J. V., and Dixon, B., 1977, Serial transplantation histology and cellular kinetics of a rat adenocarcinoma. Cell and Tissue Kinetics, 10, 583–590.

    Google Scholar 

  29. Nandi, S., and McGrath, C. M., 1973, Mammary neoplasia in mice. Advances in Cancer Research, 17, 353–414.

    Google Scholar 

  30. Neri, A. and Nicolson, G. L., 1981, Phenotypic drift of metastatic and cell surface properties of mammary adenocarcinoma cell clones during growth in vitro. International Journal of Cancer, 28, 731–738.

    Google Scholar 

  31. Pitelka, D. R., Hamamoto, S. T., and Taggart, B. N., 1980, Epithelial cell junctions in primary and metastatic mammary tumors of mice. Cancer Research, 40, 1588–99.

    Google Scholar 

  32. Price, J. E., Carr, D., Jones, L. D., Messer, P., and Tarin, D., 1982, Experimental analysis of factors affecting metastatic spread using naturally occurring tumours. Invasion and Metastasis, 2, 77–112.

    Google Scholar 

  33. Ringsted, J., 1957, In vitro study of a mouse mammary carcinoma simulating carcinosarcoma and sarcomatous overgrowth during transplantation. Acta pathologica et microbiologica scandinavica, 40, 373–383.

    Google Scholar 

  34. Rudland, P. S., Bennett, D., Ritter, M. A., Newman, R. A., and Warburton, M. J., 1980, Differentiation of a rat mammary stem cell line in culture. Control Mechanisms in Animal Cells, edited by L. Jiminez de Asua et al. (New York: Raven Press).

    Google Scholar 

  35. Rudland, P. S., Gusterson, B. A., Hughes, C. M., Ormerod, E. J., and Warburton, M. J., 1982, Two forms of tumors in nude mice generated by a neoplastic rat mammary cell line. Cancer Research, 42, 5196–5208.

    Google Scholar 

  36. Sanford, K., Dunn, T. B., Westfall, B. B., Covalesky, A. B., Dupree, L. T., and Earle, W. R., 1961, Sarcomatous change and maintenance of differentiation in long term cultures of mouse mammary carcinoma. Journal of The National Cancer Institute, 26, 1139–1183.

    Google Scholar 

  37. Schirrmacher, V., 1980, Shifts in tumor cell phenotypes induced by signals from the microenvironment. Relevance for the immunobiology of cancer metastasis. Immunobiology, 157, 89–98.

    Google Scholar 

  38. Shannon, J., and Pitelka, D. R., 1981, The influence of cell shape on the induction of functional differentiation in mouse mammary cells in vitro. In vitro, 17, 1016–28.

    Google Scholar 

  39. Tarin, D., and Price, J. E., 1979, Metastatic colonisation potential of primary tumour cells in mice. British Journal of Cancer, 39, 740–754.

    Google Scholar 

  40. Turner, G. A., 1982, Surface properties of the metastatic cell. Invasion and Metastasis, 2, 197–216.

    Google Scholar 

  41. Toolan, H. W., 1950, Sarcomatoid growths resulting from mammary carcinoma cells that had sojourned in immune mice. American Journal of Pathology, 26, 753–754.

    Google Scholar 

  42. Uriel, J., 1979, Retrodifferentiation and the fetal patterns of gene expression in cancer. Advances in Cancer Research, 29, 127–174.

    Google Scholar 

  43. Vaage, J., 1978, A survey of the growth characteristics of, and the host reactions to one hundred C3H/He mammary carcinomas. Cancer Research, 38, 331–338.

    Google Scholar 

  44. Vindelov, L., 1977, Flow microfluorimetric analysis of nuclear DNA in cells from solid tumours and cell suspensions. Virchows Archives B. Cellular pathology, 24, 227–242.

    Google Scholar 

  45. Wexler, H., Minton, J. P., and Ketcham, A. S., 1965, Comparison of survival time and extent of tumour metastases in mice with transplanted, induced and spontaneous tumours. Cancer, 18, 985–994.

    Google Scholar 

  46. Wylie, C. V., Nakane, P. K., and Pierce, G. B., 1973, Degree of differentiation in nonproliferating cells of mammary carcinoma. Differentiation, 1, 11–20.

    Google Scholar 

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  1. Division of Tumour Immunology, Institute of Cancer Research, Clifton Avenue, Sutton, Surrey, UK

    Susan C. Barnett & Suzanne A. Eccles

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  1. Susan C. Barnett
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  2. Suzanne A. Eccles
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Barnett, S.C., Eccles, S.A. Studies of mammary carcinoma metastasis in a mouse model system. I: Derivation and characterization of cells with different metastatic properties during tumour progression in vivo . Clin Exp Metast 2, 15–36 (1984). https://doi.org/10.1007/BF00132304

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  • DOI: https://doi.org/10.1007/BF00132304

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