Skip to main content
SpringerLink
Log in

B16 melanoma variants selected by one or more cycles of spontaneous metastasis to the same organ fail to exhibit organ specificity

  • Research Papers
  • Published:
Clinical & Experimental Metastasis Aims and scope Submit manuscript

Abstract

Metastatic clones of the mouse B16 melanoma spontaneously disseminate from subcutaneous tumors throughout the body in two stages, initially to the lungs and secondarily from established lung metastases to systemic sites. From the heterogeneous ‘parent’ B16 melanoma cell line and from two representative clones, G3.5 and G3.12, cell populations were selected after one or more cycles of tumor growth or metastasis to a particular site, to determine whether metastatic variants with greater organ preference or specificity could be generated. Variants with enhanced secondary metastatic activity were obtained only from G3.12 tumor-disseminated metastases growing in the lungs or in systemic organs. Regardless of the organ of selection or the number of selection cycles, all variants exhibited an overall increase in secondary metastasis incidence and burden in the brain, adrenals, kidneys and ovaries, but no organ preference or specificity was obtained. Populations that grew especially well in the brain, ovaries or liver following intravascular injection were either non-metastatic or exhibited no organ preference during spontaneous metastasis. The increased secondary metastatic activity of G3.12 variants was apparently not due to either longer host survival or to tumor-disseminated cells bypassing the lungs, but may result from enhanced growth potential or greater secondary dissemination capability imparted during growth as lung metastases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Alterman, A. L., Fornabaio, D. M., andStackpole, C. W., 1985, Metastatic dissemination of B16 melanoma: pattern and sequence of metastasis.Journal of the National Cancer Institute,75, 691–702.

    Google Scholar 

  2. Alterman, A. L., andStackpole, C. W., 1989, B16 melanoma spontaneous brain metastasis: occurrence and development within leptomeninges blood vessels.Clinical and Experimental Metastasis,7, 15–23.

    Google Scholar 

  3. Brodt, P., 1986, Characterization of two highly metastatic variants of Lewis lung carcinoma with different organ specificities.Cancer Research,46, 2442–2448.

    Google Scholar 

  4. Brunson, K. W., Beattie, G., andNicolson, G. L., 1978, Selection and altered properties of brain-colonising metastatic melanoma.Nature,272, 543–545.

    Google Scholar 

  5. Brunson, K. W., andNicolson, G. L., 1978, Selection and biologic properties of malignant variants of a murine lymphosarcoma.Journal of the National Cancer Institute,61, 1499–1503.

    Google Scholar 

  6. Brunson, K. W., andNicolson, G. L., 1979, Selection of malignant melanoma variant cell lines for ovary colonization.Journal of Supramolecular Structure,11, 517–528.

    Google Scholar 

  7. Cavanaugh, P. G., andNicolson, G. L., 1989, Purification and some properties of a lung-derived growth factor that differentially stimulates the growth of tumor cells metastatic to the lung.Cancer Research,49, 3928–3933.

    Google Scholar 

  8. Fidler, I. J., 1973, Selection of successive tumor lines for metastasis.Nature,242, 148–149.

    Google Scholar 

  9. Hart, I. R., andFidler, I. J., 1980, Role of organ selectivity in the determination of metastatic patterns of B16 melanoma.Cancer Research,40, 2281–2287.

    Google Scholar 

  10. Kim, U., 1986, Pathogenesis and characteristics of spontaneously metastasizing mammary carcinomas and the general principle of metastasis,Journal of Surgical Oncology,33, 151–165.

    Google Scholar 

  11. Matzku, S., Komitowski, D., Mildenberger, M., andZöller, M., 1983, Characterization of BSp73, a spontaneous rat tumor and itsin vivo selected variants showing different metastasizing capacities.Invasion and Metastasis,3, 109–123.

    Google Scholar 

  12. Miner, K. M., Kawaguchi, T., Uba, G. W., andNicolson, G. L., 1982, Clonal drift of cell surface, melanogenic, and experimental metastatic properties ofin vivo-selected, brain meninges-colonizing murine B16 melanoma.Cancer Research,42, 4631–4638.

    Google Scholar 

  13. Netland, P. A., andZetter, B. R., 1984, Organ-specific adhesion of metastatic tumor cellsin vitro.Science,224, 1113–1115.

    Google Scholar 

  14. Nicolson, G. L., 1988, Organ specificity of tumor metastasis: role of preferential adhesion, invasion and growth of malignant cells at specific secondary sites.Cancer Metastasis Reviews,7, 143–188.

    Google Scholar 

  15. Nicolson, G. L., Brunson, K. W., andFidler, I. J., 1978, Specificity of arrest, survival, and growth of selected metastatic variant cell lines.Cancer Research,38, 4105–4111.

    Google Scholar 

  16. Nicolson, G. L., Dulski, K., Basson, C., andWelch, D. R., 1985, Preferential organ attachment and invasionin vitro by B16 melanoma cells selected for differing metastatic colonization and invasive properties.Invasion and Metastasis,5, 144–158.

    Google Scholar 

  17. Nicolson, G. L., Mascali, J. J., andMcGuire, E. J., 1982, Metastatic RAW117 lymphosarcoma as a model for malignant-normal cell interactions. Possible roles for cell surface antigens in determining the quantity and location of secondary tumors.Oncodevelopment in Biological Medicine,4, 149–159.

    Google Scholar 

  18. Nicolson, G. L., andWinkelhake, J. L., 1975, Organ specificity of blood-borne tumor metastasis determined by cell adhesion?Nature,255, 230–232.

    Google Scholar 

  19. Paget, S., 1889, The distribution of secondary growths in cancer of the breast.Lancet,1, 571–573.

    Google Scholar 

  20. Pál, K., Kopper, L., andLapis, K., 1983, Increased metastatic capacity of Lewis lung tumor cells byin vivo selection procedure.Invasion and Metastasis,3, 174–182.

    Google Scholar 

  21. Pauli, B. U., andLee, C.-L., 1988, Organ preference of metastasis. The role of organ-specifically modulated endothelial cells.Laboratory Investigation,58, 379–387.

    Google Scholar 

  22. Raz, A., andHart, I. R., 1980, Murine melanoma: a model for intracranial metastasis.British Journal of Cancer,42, 331–341.

    Google Scholar 

  23. Sargent, N. S. E., Oestreicher, M., Haidvogl, H., Madnick, H. M., andBurger, M. M., 1988, Growth regulation of cancer metastases by their host organ.Proceedings of the National Academy of Sciences, U.S.A.,85, 7251–7255.

    Google Scholar 

  24. Schirrmacher, V., Shantz, G., Clauer, K., Komitowski, D., Zimmermann, H.-P., andLohmann-Matthes, M.-L., 1979, Tumor metastases and cell-mediated immunity in a model system in DBA/2 mice. I. Tumor invasivenessin vitro and metastasis formationin vivo.International Journal of Cancer,23, 233–244.

    Google Scholar 

  25. Shearman, P. J., andLongenecker, B. M., 1980, Selection for virulence and organ-specific metastasis of herpesvirus-transformed lymphoma cells.International Journal of Cancer,25, 363–369.

    Google Scholar 

  26. Stackpole, C. W., 1983, Generation of phenotypic diversity in the B16 mouse melanoma relative to spontaneous metastasis.Cancer Research,43, 3057–3065.

    Google Scholar 

  27. Stackpole, C. W., Alterman, A. L., andFornabaio, D. M., 1985, Growth characteristics of clonal cell populations constituting a B16 melanoma metastasis model system.Invasion and Metastasis,5, 125–143.

    Google Scholar 

  28. Stackpole, C. W., Alterman, A. L., andFornabaio, D. M., 1986, Metastasis of the B16 melanoma: experimental strategies for identifying the metastatic cell phenotype.Cancer Reviews,5, 83–117.

    Google Scholar 

  29. Sugarbaker, E. V., 1981, Patterns of metastasis in human malignancies.Cancer Biology Reviews,2, 235–278.

    Google Scholar 

  30. Tao, T.-W. Matter, A., Vogel, K., andBurger, M. M., 1979, Liver colonizing melanoma cells selected from B16 melanoma.International Journal of Cancer,23, 854–857.

    Google Scholar 

  31. Weiss, L., Ward, P. M., Harlos, J.-P., andHolmes, J. C., 1984, Target organ patterns of tumors in mice following the arterial dissemination of B16 melanoma cells.International journal of Cancer,33, 825–830.

    Google Scholar 

  32. Willis, R. A., 1973,The Spread of Tumours in the Human Body, 3d ed (London: Butterworth).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, New York Medical College, 10595, Valhalla, NY, USA

    C. W. Stackpole, A. L. Alterman & E. F. Valle

Authors
  1. C. W. Stackpole
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. L. Alterman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E. F. Valle
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Stackpole, C.W., Alterman, A.L. & Valle, E.F. B16 melanoma variants selected by one or more cycles of spontaneous metastasis to the same organ fail to exhibit organ specificity. Clin Exp Metast 9, 319–332 (1991). https://doi.org/10.1007/BF01753733

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01753733

Keywords

Search

Navigation