Skip to main content

Advertisement

Log in

Growth and metastatic behavior of human tumor cells implanted into nude and beige nude mice

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

The growth and metastatic behavior of several human tumor lines grown in adult nude mice, nude mice pretreated with antiserum against asialo GM1 glycoprotein, and beige nude mice were studied. The cell lines were all injected s.c. and i.v. A human colon carcinoma line was also injected into the spleen, and two human renal carcinoma lines were injected into renal subcapsule. All the tumor lines grew as fast or faster in adult nude mice compared with beige nude mice. There were no discernible differences in the production of experimental lung metastasis among the three groups of mice, but human colorectal carcinoma cells and human renal carcinoma cells produced more metastases in nude mice than in beige nude mice after intrasplenic or renal subcapsule injection, respectively. In vitro cytotoxicity assays confirmed that adult nude mice had high levels of natural killer (NK) cell activity whereas nude mice pretreated with anti-asialo GM1 serum and beige nude mice did not. The in vitro NK cell activity of nude mice was demonstrable against mouse lymphoma cells but not against human leukemia cells which were sensitive to lysis by human NK cells. These results suggest that the implantation of human tumor cells into beige nude mice, which are deficient in NK cell activity does not provide an advantageous model for the study of growth and metastasis of human neoplasms.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

NK:

natural killer

HCC:

human colon carcinoma

HRCC:

human renal cell carcinoma

anti-asGM1:

anti-asialo GM1

i.s.:

intrasplenic

RSC:

renal subcapsule

HBSS:

Ca2+- and Mg2+-free Hanks' balanced salt solution

References

  1. Akagawa, K. S., Maruyama, Y., Takano, M., Kasai, M., and Tokunaga, T., 1981, A cell surface antigen expressed on mouse lung macrophages. Microbiology and Immunology, 25, 1215–1220.

    Google Scholar 

  2. Barlozzari, T., Reynolds, C. W., and Herberman, R. B., 1983, In vivo role of natural killer cells: Involvement of large granular lymphocytes in the clearance of tumor cells in anti-asialo GM1-treated rats. The Journal of Immunology, 131, 1024–1027.

    Google Scholar 

  3. Barlozzari, T., Leomhardt, J., Wiltrout, R. H., Herberman, R. B., and Reynolds, C. W., 1985, Direct evidence for the role of LGL in the inhibition of experimental tumor metastases. The Journal of Immunology, 134, 2783–2789.

    Google Scholar 

  4. Cikes, M., Friberg, S. Jr., and Klein, G., 1973, Progressive loss of H-2 antigen(s) determined by Moloney leukemia virus in cultured murine lymphomas. Journal of the National Cancer Institute, 50, 347–362.

    Google Scholar 

  5. Fidler, I. J., Pollack, V. A., and Hanna, N., 1984, The use of nude mice for studies of cancer metastasis. Immune Deficient Animals, edited by B. Sordat (Basel: Karger A. G.), pp. 328–338.

    Google Scholar 

  6. Fidler, I. J., and Kirpke, M. L., 1980, Tumor cell antigenicity, host immunity and cancer metastasis. Cancer Immunology and Immunotherapy, 7, 201–205.

    Google Scholar 

  7. Fidler, I. J., 1975, Biological behavior of malignant melanoma cells correlated to their survival in vivo. Cancer Research, 35, 218–224.

    Google Scholar 

  8. Fodstad, Ø., Hansen, C. T., Cannon, G. B., Statham, C. N., Lichtenstein, G. R., and Boyd, M. R., 1984, Lack of correlation between natural killer activity and tumor growth control in nude mice with different immune defects. Cancer Research, 44, 4403–4408.

    Google Scholar 

  9. Frost, P., Smith, J., and Frost, H., 1978, The radiolabeling of lymphocytes and tumor cells with 111Indium. Proceedings of the Society for Experimental Biology and Medicine, 157, 61–67.

    Google Scholar 

  10. Giavazzi, R., Campbell, D. E., Jessup, J. M., Cleary, K., and Fidler, I. J., 1986, Metastatic behavior of tumor cells isolated from primary and metastatic human colorectal carcinoma implanted into athymic nude mice. Cancer Research, 46, 1928–1933.

    Google Scholar 

  11. Hanna, N., 1982, Role of natural killer cells in control of cancer metastasis. Cancer and Metastasis Reviews, 1, 45–64.

    Google Scholar 

  12. Hanna, N., 1980, Expression of metastatic potential of tumor cells in young nude mice is correlated with low levels of natural killer cell-mediated cytotoxicity. International Journal of Cancer, 26, 675–680.

    Google Scholar 

  13. Hanna, N., and Fidler, I. J., 1980, Role of natural killer cells in the destruction of circulating tumor emboli. Journal of the National Cancer Institute, 65, 801–809.

    Google Scholar 

  14. Hanna, N., and Fidler, I. J., 1981, Relationship between metastatic potential and resistance to natural killer cell-mediated cytotoxicity in three murine tumor systems. Journal of the National Cancer Institute, 66, 1183–1190.

    Google Scholar 

  15. Hanna, N., and Fidler, I. J., 1981, Expression of metastatic potential of allogeneic and xenogeneic neoplasms in young nude mice. Cancer Research, 41, 438–444.

    Google Scholar 

  16. Hanna, N., and Schneider, M., 1983, Enhancement of tumor metastasis and suppression of natural killer cell activity by β-estradiol treatment. The Journal of Immunology, 130, 974–980.

    Google Scholar 

  17. Hansson, M., Karre, K., Bakacs, T., Kiessling, R., and Klein, G., 1978, Intra- and interspecies reactivity of human and mouse natural killer (NK) cells. The Journal of Immunology, 121, 6–12.

    Google Scholar 

  18. Jondal, M., and Pross, H., 1975, Surface markers on human B- and T-lymphocytes. VI. Cytotoxicity against cell lines as a functional marker for lymphocyte subpopulations. International Journal of Cancer, 15, 596–605.

    Google Scholar 

  19. Karre, K., Klein, G. O., Kiessling, R., and Roder, J. C., 1980, Low natural in vivo resistance to syngeneic leukemias in natural killer-deficient mice. Nature, 284, 624–626.

    Google Scholar 

  20. Karre, K., Klein, G. O., Kiessling, R., Klein, G., and Roder, J. C., 1980, In vitro NK activity and in vivo resistance to leukemia: Studies of beige, beige nude and wild-type hosts on C57BL background. International Journal of Cancer, 26, 789–797.

    Google Scholar 

  21. Kasai, M., Yoneda, T., Habu, S., Maruyama, Y., Okumura, K., and Tokunaga, T., 1981, In vivo effect of anti-asialo GM1 antibody on natural killer activity. Nature, 291, 334–335.

    Google Scholar 

  22. Kcozlowski, J. M., Fidler, I. J., Campbell, D., Xu, Z., Kaighn, M. E., and Hart, I. R., 1984, Metastatic behavior of human tumor cell lines grown in the nude mouse. Cancer Research, 44, 3522–3529.

    Google Scholar 

  23. Lozzio, C. B., and Lozzio, B. B., 1975, Human chronic myelogenous leukemia cell line with positive Philadelphia chromosome. Blood, 45, 321–334.

    Google Scholar 

  24. Naito, S., Von Eschenbech, A. C., Giavazzi, R., and Fidler, I. J., 1986, Growth and metastasis of tumor cells isolated from a human renal cell carcinoma implanted into different organs of nude mice. Cancer Research, 46, 4109–4115.

    Google Scholar 

  25. Reid, L. C. M., and Shin, S., 1978, Transplantation of heterologous endocrine tumor cells in nude mice. The Nude Mouse in Experimental and Clinical Research, edited by J. Fogh and B. C. Giovanella (New York: Academic Press), pp. 313–348.

    Google Scholar 

  26. Riccardi, C., Puccetti, P., Santoni, A., and Herberman, R. B., 1979, Rapid to vivo assay of mouse natural killer cell activity. Journal of the National Cancer Institute, 63, 1041–1045.

    Google Scholar 

  27. Riccardi, C., Santoni, A., Barlozzari, T., Puccetti, P., and Herberman, R. B., 1980, In vitro natural reactivity of mice against tumor cells. International Journal of Cancer, 25, 475–486.

    Google Scholar 

  28. Riccardi, C., Santoni, A., Barlozzari, T., and Herberman, R. B., 1980, Role of NK cells in rapid in vivo clearance of radiolabeled tumor cells. Natural Cell-Mediated Immunity against Tumors, edited by R. B. Herberman (New York: Academic Press), pp. 1121–1139.

    Google Scholar 

  29. Roder, J., and Duwe, A., 1979, The beige mutation in the mouse selectivity impairs natural killer cell function. Nature, 278, 451–453.

    Google Scholar 

  30. Sharkey, F. E., and Fogh, J., 1984, Consideration in the use of nude mice for cancer research. Cancer and Metastasis Reviews, 3, 341–360.

    Google Scholar 

  31. Shimanura, K., Maruo, K., Ueyama, Y., Habu, S., Okumura, K., and Tamaoki, N., 1984, Role of NK cells in solid tumor metastasis in beige, nude mice and normal mice. Immune-Deficient Animals, 4th International Workshop on Immune-Deficient Animals in Experimental Research, Chexbres 1982, (Basel: Karger), pp. 353–356.

    Google Scholar 

  32. Sordat, B., Merenda, C., and Carrel, S., 1977, Invasive growth and dissemination of human solid tumors and malignant cell lines grafted subcutaneously to newborn nude mice. Proceedings of the Second International Workshop on Nude Mice, edited by T. Nomura, N. Ohsawa, N. Tamaoki and R. Fujiwara (Tokyo: University of Tokyo Press), pp. 311–326.

    Google Scholar 

  33. Talmage, J. E., Meyers, K. M., Prieur, D. J., and Starkey, J. R., 1980, Role of NK cells in tumor growth and metastasis in beige mice. Nature, 284, 622–624.

    Google Scholar 

  34. Urdal, D. L., Kawase, I., and Henney, C. S., 1982, NK cell-target interactions: Approaches toward definition of recognition structures. Cancer and Metastasis Reviews, 1, 65–83.

    Google Scholar 

  35. Wiltrout, R. H., Frost, P., and Cummings, G. D., 1978, Isotope release cytotoxic activity with the use of Indium-111: advantage over chromium-51 in long-term assays. Journal of the National Cancer Institute, 61, 183–195.

    Google Scholar 

  36. Windhorst, D. B., and Pagett, D., 1973, The Chediak-Higashi syndrome and the homologous trait in animals, Journal of Investigative Dermatology, 60, 529–537.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Naito, S., Giavazzi, R., Walker, S.M. et al. Growth and metastatic behavior of human tumor cells implanted into nude and beige nude mice. Clin Exp Metast 5, 135–146 (1987). https://doi.org/10.1007/BF00058059

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00058059

Keywords

Navigation