Summary
We found that the number of pulmonary metastatic foci of spontaneously developed rat mammary carcinoma (SST-2), when transplanted subcutaneously in spontaneously hypertensive (SH) rats, decreased with aging.
In the SST-2-bearing SH rats, it was observed that T cell functions progressively declined while activities of macrophages and natural killer cells were non-specifically activated by increasing age. To examine the mechanisms of the age-related decrease of pulmonary metastasis in SH rats, we treated the SST-2-bearing rats with anti-(asialo-GM1) antibody and/or carrageenan, which are known to suppress the functions of macrophages and natural killer cells, or with poly(I) · poly(C), which is a stimulator to natural killer cells. The anti-(asialo-GM1) treatment significantly increased the number of pulmonary metastatic foci in both young and old SH rats, while poly(I) · poly(C) significantly decreased the lung nodules in the old SH rats. These results suggest that the decrease of pulmonary metastasis in the SH rats with aging may be closely correlated with non-specifically activated natural killer cells and macrophages, though it should be also considered that non-immunological tumor-host interactions may be involved in the differences between the young and the old SH rats.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ershler WB, Stewart JA, Hacker MP, Moore AL, Tindle BH (1984) B16 murine melanoma and aging: slower growth and longer survival in old mice. J Natl Cancer Inst 72: 161–164
Fidler IJ, Poste G (1982) Macrophage mediated destruction of malignant tumor cells and new strategies for the therapy of metastatic disease. Springer Semin Immunopathol 5: 161–174
Fidler IJ, Barnes Z, Fogler WE, et al. (1982) Involvement of macrophages in the eradication of established metastasis following intravenous injection of liposomes containing macrophage activators. Cancer Res 42: 496–501
Folkman J, Contran R (1976) Relation of vascular proliferation to tumor growth. Int Rev Exp Pathol 16: 207–248
Good RA (1972) Relations between immunity and malignancy. Proc Natl Acad Sci USA 69: 1026–1032
Gorelik E, Wiltrout RH, Okumura K, Habu S, Herberman RB (1982) Role of NK cells in the control of metastatic spread and growth of tumor cells in mice. Int J Cancer 30: 107
Hanna N, Burton RC (1981) Definitive evidence that natural killer (NK) cells inhibit experimental tumor metastasis in vivo. J Immunol 127: 1754
Koga Y, Hamada J, Takeichi N, Nakane A, Minagawa T, Kobayashi H (1985) Activation of natural resistance against lung metastasis of an adenocarcinoma in T-cell depressed spontaneously hypertensive rats by infection withListeria monocytogenes. Cancer Immunol Immunother 20: 103–108
Kohn RR (1983) Causes of death in very old people. JAMA 247: 2793–2797
Lutty GA, Liu SH, Prendergast RA (1983) Angiogenic lymphokines of activated T-cell origin. Invest Ophthalmol Vis Sci 24: 1595–1601
Makinodan T, Kay MM (1980) Age influence on the immune system. Adv Immunol 29: 287–330
Matsuoka T, Takeichi N, Kobayashi H (1987) Age-related changes of natural antitumor resistance in spontaneously hypertensive rats with T cell depression. Cancer Res 47: 3410–3413
Polverini PJ, Leibovich SJ (1984) Induction of neovascularization in vivo and endothelial proliferation in vitro by tumor-associated macrophages. Lab Invest 51: 635–642
Saijo N, Ozaki A, Beppu Y, Shibuya M, Shimizu E, Hoshi A (1984) Detailed analysis of artificial and spontaneous tumor metastasis in mice with depressed natural killer activity by anti-asialo GM1 antibody. In: Hoshino T, Koren HB, Uchida A (eds) Natural killer activity and its regulation. Excerpta Medica, Amsterdam, p 358
Takeichi N, Ba D, Koga Y, Kobayashi H (1983) Immunologic suppression of carcinogenesis in spontaneously hypertensive rats (SHR) with T-cell depression. J Immunol 130: 501–505
Takeichi N, Hamada J, Takimoto M, Fujiwara K, Kobayashi H (1988) Depression of T cell-mediated immunity and enhancement of antibody production by natural infection with microorganisms in spontaneously hypertensive rats (SHR). Microbiol Immunol 32: 1235–1244
Talmadge JE, Meyers KM, Prieur DJ, Starkey JR (1980) Role of natural killer cells in tumor growth and metastasis: C57BL/6 normal and beige mice. J Natl Cancer Inst 65: 929–935
Tsuda T, Kim YT, Siskind GW, Weksler ME (1987) Role of the thymus and T-cells in slow growth of B16 melanoma in old mice. Cancer Res 47: 3097–3100
Yunis EJ, Fernandes GM, Stutman O (1976) Susceptibility to involution of the thymus-dependent lymphoid system and autoimmunity. Am J Clin Pathol 56: 280–292
Author information
Authors and Affiliations
Additional information
Supported in part by a grant-in-aid for cancer research from the Japanese Ministry of Education, Culture and Science.
Rights and permissions
About this article
Cite this article
Takeichi, N., Li, X., Hamada, Ji. et al. Age-related decrease of pulmonary metastasis of rat mammary carcinoma by activated natural resistance. Cancer Immunol Immunother 31, 81–85 (1990). https://doi.org/10.1007/BF01742370
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01742370