Identification of modifiable risk factors which contribute to tumour metastasis is an important goal of cancer prevention research. This study was designed to evaluate the role of moderate exercise conditioning on the in vivo retention of radiolabelled H-ras-transformed fibroblasts (CIRAS 1 and CIRAS 3 cell lines) in mice with (C3H/He-bg 2J/+) and without (C3H/HeJ) the beige (bg) mutation which produces impaired natural killer (NK) cell function. Mice were randomly assigned to treadmill training (20 m/min, 30 min/day, 5 times/week) or remained sedentary for 9 weeks. C3H beige mice had significantly higher retention in the lungs of CIRAS 1 tumour cells (P < 0.0001) than genotypically normal C3H/HeJ mice. There was a significant main effect of exercise conditioning (P<0.05) with trained mice (irrespective of genotype) having lower tumour retention (44±3%) than sedentary controls (53±3%). Comparing the in vivo retention of LIRAS 1 and LIRAS 3 in the lungs of genotypically normal mice, we observed higher retention of CIRAS 1 (48±2%, compared with 18±2% for CIRAS 3; P<0.0001). There was a significant interaction effect of exercise and tumour type (P<0.05): trained mice had a lower retention for CIRAS 1 than sedentary controls (43±3%, compared with 53±3%), while training status had no effect on CIRAS 3 retention. There were no significant differences in final tumour multiplicity in the lung as a function of exercise condition. The data suggest that exercise conditioning reduces some measures of in vivo burden but only for the less aggressive tumour variant (CIRAS 1); further, innate immune mechanisms other than NK cells are likely to be involved in this modest protective effect.
Similar content being viewed by others
References
Hoffman-Goetz, L and Husted, J, 1994, Exercise and breast cancer: review and critical analysis of the literature. Can J Appl Physiol, 19, 237–52.
Hoffman-Goetz, L and Husted, J, 1995, Exercise and cancer: do the biology and epidemiology correspond? Exerc Immunol Rev, 1, 81–96.
Sternfeld, B, 1992, Cancer and the protective effect of physical activity: the epidemiological evidence. Med Sci Sports Exerc, 24, 1195–209.
Adrianopoulos, G, Nelson, RL, Bombeck, CT and Souza, G, 1987, The influence of physical activity in 1,2-dimethylhydrazine induced colon carcinogenesis in the rat. Anticancer Res, 7, 849–52.
Lee, IM and Paffenbarger, RS, Jr, 1994, Physical activity and risk of developing colorectal cancer among college alumni. Med Sci Sports Exerc, 26, 831–7.
Bernstein, L, Henderson, BE, Hanisch, R, Sullivan Halley, J and Ross, RK, 1994, Physical exercise and reduced risk of breast cancer in young women. J Natl Cancer Inst, 86, 1403–8.
Thompson HJ, 1994, Effect of exercise intensity and duration on the induction of mammary carcinogenesis. Cancer Res, 54, 1960–3s.
Cohen, LA, Choi, K and Wang, CX, 1988, Influence of dietary fat, caloric restriction, and voluntary exercise on N nitrosomethylurea induced mammary tumorigenesis in rats. Cancer Res, 48, 4276–83.
Hoffman-Goetz, L and Pedersen, BK, 1994, Exercise and the immune system: a model of the stress response? Immunol Today, 15, 382–7.
Uhlenbruck, G and Order, U, 1991, Can endurance sports stimulate immune mechanisms against cancer and metastasis? Int J Sports Med, 12, S53–68.
Nieman, DC, Miller, AR, Henson, DA, et al. 1993, Effects of high- vs moderate-intensity exercise on natural killer cell activity. Med Sci Sports Exerc, 25, 1126–34.
Pedersen, BK, Tvede, N, Hansen, FR, et al. 1988, Modulation of natural killer cell activity in peripheral blood by physical exercise. Scand J Immunol, 27, 673–8.
Nieman, DC, Nehlsen Cannarella, SL, Markoff, PA, et al. 1990, The effects of moderate exercise training on natural killer cells and acute upper respiratory tract infections. Int J Sports Med, 11, 467–73.
Pedersen, BK, Tvede, N, Christensen, LD, Klarlund, K, Kragbak, S and Halkjær Kristensen, J, 1989, Natural killer cell activity in peripheral blood of highly trained and untrained persons. Int J Sports Med, 10, 129–31.
MacNeil, B and Hoffman-Goetz, L, 1993, Chronic exercise enhances in vivo and in vitro cytotoxic mechanisms of natural immunity in mice. J Appl Physiol, 74, 388–95.
Hoffman-Goetz, L, May, KM and Arumugam, Y, 1994, Exercise training and mouse mammary tumour metastasis. Anticancer Res, 14, 2627–32.
MacNeil, B and Hoffman-Goetz, L, 1993, Exercise training and tumour metastasis in mice: influence of time of exercise onset. Anticancer Res, 13, 2085–8.
Srere, PA, 1969, Citrate synthase. Methods Enzymol, 13, 3–5.
Egan, SE, McCarty, GA, Jarolim, L, et al. 1987, Expression of H-ras correlates with metastatic potential: evidence for direct regulation of the metastatic phenotype in 10T% MathType!MTEF!2!1!+-% feaafiart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn% hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr% 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq-Jc9% vqaqpepm0xbba9pwe9Q8fs0-yqaqpepae9pg0FirpepeKkFr0xfr-x% fr-xb9adbaqaaeGaciGaaiaabeqaamaabaabaaGcbaWaaSqaaSqaai% aaigdaaeaacaaIYaaaaaaa!3780!\[\tfrac{1}{2}\] and NIH 3T3 cells. Mol Cell Biol, 7, 830–7.
Wiltrout, RH, Gorelik, E, Brunda, MJ, Holden, HT and Herberman, RB, 1983, Assessment of in vivo natural antitumor resistance and lymphocyte migration in mice: comparison of 125I-iododeoxyuridine with 111indium oxine and 51chromium as cell labels. Cancer Immunol Immunother, 14, 172–9.
Roder, JC and Duwe, A, 1979, The beige mutation in the mouse selectively impairs natural killer cell function. Nature, 278, 451–3.
Hoffman-Goetz, L, MacNeil, B and Arumugam, Y, 1993, Tissue distribution of radiolabelled tumor cells in wheel exercised and sedentary mice. Int J Sports Med, 15, 249–53.
Hasday, JD, Shah, EM and Lieberman, AP, 1990, Macrophage tumor necrosis factor a release is induced by contact with some tumors. J Immunol, 145, 371–9.
Rhind, SG, Shek, PN and Shephard, RJ, 1995, The impact of exercise on cytokines and receptor expression. Exerc Immunol Rev, 1, 97–148.
Duerksen Hughes, PJ and Gooding, LR. Macrophage mediated cytotoxicity. In: Sitkovsky, MV, Kenkary PA, eds. Cytotoxic Cells, Recognition, Effector Function, Generation, and Methods. Boston: Birkhauser, 1993, pp. 439–54.
Mahoney, KH, Fulton, AM and Heppner, GH, 1983, Tumor associated macrophages of mouse mammary tumors. II. Differential distribution of macrophages from metastatic and nonmetastatic tumors. J Immunol, 131, 2079–85.
Greenberg, AH, Egan, SE, Jarolim, L, Gingras, M-C and Wright, JA, 1987, Natural killer cell regulation of implantation and early lung growth of H-ras-transformed % MathType!MTEF!2!1!+-% feaafiart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn% hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr% 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq-Jc9% vqaqpepm0xbba9pwe9Q8fs0-yqaqpepae9pg0FirpepeKkFr0xfr-x% fr-xb9adbaqaaeGaciGaaiaabeqaamaabaabaaGcbaWaaSqaaSqaai% aaigdaaeaacaaIYaaaaaaa!3780!\[\tfrac{1}{2}\] fibroblasts in mice. Cancer Res, 47, 4801–5.
Spreafico, F and Garattini, S. Chemotherapy of experimental metastasis. In: Baldwin, RW, ed. Secondary Spread of Cancer. New York: Academic Press, 1978, pp. 101–29.
Wiltrout, RH. The use of preclinical rodent models for cancer immunotherapy. In: Gallagher, G, Rees, RC and Reynolds, CW, eds. Tumour Immunobiology: A Practical Approach. Oxford: Oxford University Press, 1993, pp. 369–83.
Hoffman-Goetz L, 1995, Effect of acute treadmill exercise on LFA 1 antigen expression in murine splenocytes. Anticancer Res, 15.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Jadeski, L., Hoffman-Goetz, L. Exercise and in vivo natural cytotoxicity against tumour cells of varying metastatic capacity. Clin Exp Metast 14, 138–144 (1996). https://doi.org/10.1007/BF00121210
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00121210