Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1984 Apr;49(4):415–421. doi: 10.1038/bjc.1984.67

Heterogeneity in a spontaneous mouse lung carcinoma: selection and characterisation of stable metastatic variants.

M G Layton, L M Franks
PMCID: PMC1976760  PMID: 6324836

Abstract

The development and characterisation of a new epithelial model for the experimental investigation of metastasis is described. A tissue culture cell line CMT64 was established from a spontaneous alveolar lung carcinoma of a 17 month old female C57BL/ICRF at mouse (Franks et al., 1976). Subcutaneous inoculation of cells produces local tumours which give rise to a small number of lung metastases within three weeks. Four different tissue culture sublines CMT167, 170, 175 and 181 with increased metastatic ability were selected from pooled lung metastases by culture, mouse inoculation and reselection from lung metastases through four culture/inoculation cycles. These sublines are themselves heterogeneous and clones derived from them display marked differences in metastatic behaviour. Both CMT64 and its sublines have remained relatively stable in morphology and behavior since their origin, are fairly well differentiated, produce basal lamina even in metastases, and metastasise rapidly and preferentially to the lung after subcutaneous and intravenous inoculation in both syngeneic C57 and Nu/Nu mice (Franks & Layton, 1984). The expression of the metastatic potential of these cells is strongly influenced by the age and immune status of the host. The CMT64 system is a particularly useful model for experimental metastasis studies.

Full text

PDF
415

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Chen T. R. In situ detection of mycoplasma contamination in cell cultures by fluorescent Hoechst 33258 stain. Exp Cell Res. 1977 Feb;104(2):255–262. doi: 10.1016/0014-4827(77)90089-1. [DOI] [PubMed] [Google Scholar]
  2. Fidler I. J., Cifone M. A. Properties of metastatic and nonmetastatic cloned subpopulations of an ultraviolet-light-induced murine fibrosarcoma of recent origin. Am J Pathol. 1979 Dec;97(3):633–648. [PMC free article] [PubMed] [Google Scholar]
  3. Fidler I. J., Gersten D. M., Riggs C. W. Relationship of host immune status to tumor cell arrest, distribution, and survival in experimental metastasis. Cancer. 1977 Jul;40(1):46–55. doi: 10.1002/1097-0142(197707)40:1<46::aid-cncr2820400110>3.0.co;2-t. [DOI] [PubMed] [Google Scholar]
  4. Fidler I. J., Hart I. R. Biological and experimental consequences of the zonal composition of solid tumors. Cancer Res. 1981 Aug;41(8):3266–3267. [PubMed] [Google Scholar]
  5. Franks L. M., Carbonell A. W., Hemmings V. J., Riddle P. N. Metastasizing tumors from serum-supplemented and serum-free cell lines from a C57BL mouse lung tumor. Cancer Res. 1976 Mar;36(3):1049–1055. [PubMed] [Google Scholar]
  6. Franks L. M., Layton M. G. Ultrastructural tumour differentiation and organ specificity in high and low metastatic lines from a mouse lung carcinoma. Br J Cancer. 1984 Apr;49(4):423–429. doi: 10.1038/bjc.1984.68. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hanna N. Role of natural killer cells in control of cancer metastasis. Cancer Metastasis Rev. 1982;1(1):45–64. doi: 10.1007/BF00049480. [DOI] [PubMed] [Google Scholar]
  8. Hart I. R., Fidler I. J. The implications of tumor heterogeneity for studies on the biology of cancer metastasis. Biochim Biophys Acta. 1981 Aug 31;651(1):37–50. doi: 10.1016/0304-419x(81)90004-4. [DOI] [PubMed] [Google Scholar]
  9. Neri A., Welch D., Kawaguchi T., Nicolson G. L. Development and biologic properties of malignant cell sublines and clones of a spontaneously metastasizing rat mammary adenocarcinoma. J Natl Cancer Inst. 1982 Mar;68(3):507–517. [PubMed] [Google Scholar]
  10. Poste G., Doll J., Brown A. E., Tzeng J., Zeidman I. Comparison of the metastatic properties of B16 melanoma clones isolated from cultured cell lines, subcutaneous tumors, and individual lung metastases. Cancer Res. 1982 Jul;42(7):2770–2778. [PubMed] [Google Scholar]
  11. Poste G., Doll J., Fidler I. J. Interactions among clonal subpopulations affect stability of the metastatic phenotype in polyclonal populations of B16 melanoma cells. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6226–6230. doi: 10.1073/pnas.78.10.6226. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Poste G. Experimental systems for analysis of the malignant phenotype. Cancer Metastasis Rev. 1982;1(2):141–199. doi: 10.1007/BF00048224. [DOI] [PubMed] [Google Scholar]
  13. Poste G., Fidler I. J. The pathogenesis of cancer metastasis. Nature. 1980 Jan 10;283(5743):139–146. doi: 10.1038/283139a0. [DOI] [PubMed] [Google Scholar]
  14. Prehn R. T., Lappé M. A. An immunostimulation theory of tumor development. Transplant Rev. 1971;7:26–54. doi: 10.1111/j.1600-065x.1971.tb00462.x. [DOI] [PubMed] [Google Scholar]
  15. Rowlatt C., Franks L. M., Sheriff M. U., Chesterman F. C. Naturally occurring tumors and other lesions of the digestive tract in untreated C57BL mice. J Natl Cancer Inst. 1969 Dec;43(6):1353–1364. [PubMed] [Google Scholar]
  16. Skov C. B., Holland J. M., Perkins E. H. Development of fewer tumor colonies in lungs of athymic nude mice after intravenous injection of tumor cells. J Natl Cancer Inst. 1976 Jan;56(1):193–195. doi: 10.1093/jnci/56.1.193. [DOI] [PubMed] [Google Scholar]
  17. Stackpole C. W. Distinct lung-colonizing and lung-metastasizing cell populations in B16 mouse melanoma. Nature. 1981 Feb 26;289(5800):798–800. doi: 10.1038/289798a0. [DOI] [PubMed] [Google Scholar]
  18. Steele J. G., Rowlatt C., Sandall J. K., Franks L. M. Cell surface properties of high- and low-metastatic cell lines selected from a spontaneous mouse lung carcinoma. Int J Cancer. 1983 Dec 15;32(6):769–779. doi: 10.1002/ijc.2910320619. [DOI] [PubMed] [Google Scholar]
  19. Talmadge J. E. The selective nature of metastasis. Cancer Metastasis Rev. 1983;2(1):25–40. doi: 10.1007/BF00046904. [DOI] [PubMed] [Google Scholar]
  20. Weiss L., Holmes J. C., Ward P. M. Do metastases arise from pre-existing subpopulations of cancer cells? Br J Cancer. 1983 Jan;47(1):81–89. doi: 10.1038/bjc.1983.10. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Wexler H. Accurate identification of experimental pulmonary metastases. J Natl Cancer Inst. 1966 Apr;36(4):641–645. doi: 10.1093/jnci/36.4.641. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES