Skip to main content

Advertisement

Log in

Physical exercise effects on metastasis: a systematic review and meta-analysis in animal cancer models

  • Published:
Cancer and Metastasis Reviews Aims and scope Submit manuscript

Abstract

Physical exercise is considered a well-tolerated adjuvant therapy to mitigate cancer-related side effects, but its impact on metastasis is unclear. The present systematic review and meta-analysis aimed to summarize the evidence on the effects of exercise on metastasis in animal cancer models. A systematic search was conducted to identify controlled studies in animals analyzing the impact of exercise interventions on any marker of metastasis incidence or severity. The pooled mean differences (PMD) were calculated for those endpoints for which a minimum of three studies used the same assessment method. We also calculated the pooled odds ratio (OR) of metastases. Twenty-six articles were included in the systematic review, of which 12 could be meta-analyzed. Exercise training in murine cancer models did not significantly modify the number of metastatic foci (PMD = − 3.18; 95% confidence interval [CI] − 8.32, 1.97; p = 0.23), the weight of metastatic tumors (PMD = − 0.03; 95% CI − 0.10, 0.04; p = 0.41), or the risk of developing metastasis (OR = 0.64; 95% CI 0.10, 4.12; p = 0.64). These findings suggest that exercise has no overall influence on any marker of cancer metastasis incidence or severity in animal models. However, the wide methodological heterogeneity observed between studies might be taken into account and the potential exercise effects on metastasis development remain to be determined in pediatric tumors.

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.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Steeg, P. S. (2016). Targeting metastasis. Nature Reviews Cancer, 16, 201–218. https://doi.org/10.1038/nrc.2016.25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Lambert, A. W., Pattabiraman, D. R., & Weinberg, R. A. (2017). Emerging biological principles of metastasis. Cell, 168, 670–691. https://doi.org/10.1016/j.cell.2016.11.037.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Nguyen, D. X., Bos, P. D., & Massagué, J. (2009). Metastasis: from dissemination to organ-specific colonization. Nature Reviews Cancer, 9, 274–284. https://doi.org/10.1038/nrc2622.

    Article  CAS  PubMed  Google Scholar 

  4. Massagué, J., & Obenauf, A. C. (2016). Metastatic colonization by circulating tumour cells. Nature, 529, 298–306. https://doi.org/10.1038/nature17038.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Pedersen, L., Christensen, J. F., & Hojman, P. (2015). Effects of exercise on tumor physiology and metabolism. Cancer Journal, 21, 111–116. https://doi.org/10.1097/PPO.0000000000000096.

    Article  CAS  Google Scholar 

  6. Chen, Y. J., Li, X. X., Ma, H. K., Zhang, X., Wang, B. W., Guo, T. T., et al. (2019). Exercise training for improving patient-reported outcomes in patients with advanced-stage cancer: a systematic review and meta-analysis. Journal of Pain and Symptom Management. https://doi.org/10.1016/j.jpainsymman.2019.09.010.

  7. Schmitz, K. H., Courneya, K. S., Matthews, C., Demark-Wahnefried, W., Galvão, D. A., Pinto, B. M., Irwin, M. L., Wolin, K. Y., Segal, R. J., Lucia, A., Schneider, C. M., von Gruenigen, V., Schwartz, A. L., & American College of Sports Medicine. (2010). American College of Sports Medicine American College of Sports Medicine roundtable on exercise guidelines for cancer survivors. Medicine & Science in Sports & Exercise, 42, 1409–1426. https://doi.org/10.1249/MSS.0b013e3181e0c112.

    Article  Google Scholar 

  8. Morales, J. S., Santana-Sosa, E., Santos-Lozano, A., Baño-Rodrigo, A., Valenzuela, P. L., Rincón-Castanedo, C., et al. (2019). Inhospital exercise benefits in childhood cancer: a prospective cohort study. Scandinavian Journal of Medicine and Science in Sports. https://doi.org/10.1111/sms.13545.

  9. Morales, J. S., Valenzuela, P. L., Rincón-Castanedo, C., Takken, T., Fiuza-Luces, C., Santos-Lozano, A., & Lucia, A. (2018). Exercise training in childhood cancer: a systematic review and meta-analysis of randomized controlled trials. Cancer Treatment Reviews, 70, 154–167. https://doi.org/10.1016/j.ctrv.2018.08.012.

    Article  PubMed  Google Scholar 

  10. Fiuza-Luces, C., Padilla, J. R., Soares-Miranda, L., Santana-Sosa, E., Quiroga, J. V., Santos-Lozano, A., Pareja-Galeano, H., Sanchis-Gomar, F., Lorenzo-González, R., Verde, Z., López-Mojares, L. M., Lassaletta, A., Fleck, S. J., Pérez, M., Pérez-Martínez, A., & Lucia, A. (2017). Exercise intervention in pediatric patients with solid tumors: the physical activity in pediatric cancer trial. Medicine & Science in Sports & Exercise, 49, 223–230. https://doi.org/10.1249/MSS.0000000000001094.

    Article  Google Scholar 

  11. Schmitz, K. H., Campbell, A. M., Stuiver, M. M., Pinto, B. M., Schwartz, A. L., Morris, G. S., Ligibel, J. A., Cheville, A., Galvão, D. A., Alfano, C. M., Patel, A. V., Hue, T., Gerber, L. H., Sallis, R., Gusani, N. J., Stout, N. L., Chan, L., Flowers, F., Doyle, C., Helmrich, S., Bain, W., Sokolof, J., Winters-Stone, K. M., Campbell, K. L., & Matthews, C. E. (2019). Exercise is medicine in oncology: engaging clinicians to help patients move through cancer. CA: a Cancer Journal for Clinicians, 69, 468–484. https://doi.org/10.3322/caac.21579.

    Article  Google Scholar 

  12. Dai, J. Y., Wang, B., Wang, X., Cheng, A., Kolb, S., Stanford, J. L., & Wright, J. L. (2019). Vigorous physical activity is associated with lower risk of metastatic-lethal progression in prostate cancer and hypomethylation in the CRACR2A gene. Cancer Epidemiology, Biomarkers & Prevention, 28, 258–264. https://doi.org/10.1158/1055-9965.EPI-18-0622.

    Article  Google Scholar 

  13. Guercio, B. J., Zhang, S., Ou, F. S., Venook, A. P., Niedzwiecki, D., Lenz, H. J., Innocenti, F., O’Neil, B. H., Shaw, J. E., Polite, B. N., Hochster, H. S., Atkins, J. N., Goldberg, R. M., Sato, K., Ng, K., van Blarigan, E., Mayer, R. J., Blanke, C. D., O'Reilly, E. M., Fuchs, C. S., & Meyerhardt, J. A. (2019). Associations of physical activity with survival and progression in metastatic colorectal cancer: results from Cancer and Leukemia Group B (Alliance)/SWOG 80405. Journal of Clinical Oncology, 37, 2620–2631. https://doi.org/10.1200/JCO.19.01019.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Brown, J. C., Rhim, A. D., Manning, S. L., Brennan, L., Mansour, A. I., Rustgi, A. K., Damjanov, N., Troxel, A. B., Rickels, M. R., Ky, B., Zemel, B. S., Courneya, K. S., & Schmitz, K. H. (2018). Effects of exercise on circulating tumor cells among patients with resected stage I-III colon cancer. PLoS One, 13, e0204875. https://doi.org/10.1371/journal.pone.0204875.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Jinnah, A. H., Zacks, B. C., Gwam, C. U., & Kerr, B. A. (2018). Emerging and established models of bone metastasis. Cancers (Basel), 10. https://doi.org/10.3390/cancers10060176.

  16. Ashcraft, K. A., Peace, R. M., Betof, A. S., Dewhirst, M. W., & Jones, L. W. (2016). Efficacy and mechanisms of aerobic exercise on cancer initiation, progression, and metastasis: a critical systematic review of in vivo preclinical data. Cancer Research, 76, 4032–4050. https://doi.org/10.1158/0008-5472.CAN-16-0887.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Ruiz-Casado, A., Martín-Ruiz, A., Pérez, L. M., Provencio, M., Fiuza-Luces, C., & Lucia, A. (2017). Exercise and the hallmarks of cancer. Trends in Cancer, 3, 423–441. https://doi.org/10.1016/j.trecan.2017.04.007.

    Article  CAS  PubMed  Google Scholar 

  18. Betof, A. S., Dewhirst, M. W., & Jones, L. W. (2013). Effects and potential mechanisms of exercise training on cancer progression: a translational perspective. Brain, Behavior, and Immunity, 30, S75–S87. https://doi.org/10.1016/j.bbi.2012.05.001.

    Article  PubMed  Google Scholar 

  19. Moher, D., Shamseer, L., Clarke, M., Ghersi, D., Liberati, A., Petticrew, M., Shekelle, P., Stewart, L. A., & PRISMA-P Group. (2015). Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Systematic Reviews, 4, 1. https://doi.org/10.1186/2046-4053-4-1.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Goh, J., Tsai, J., Bammler, T. K., Farin, F. M., Endicott, E., & Ladiges, W. C. (2013). Exercise training in transgenic mice is associated with attenuation of early breast cancer growth in a dose-dependent manner. PLoS One, 8, e80123. https://doi.org/10.1371/journal.pone.0080123.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Hooijmans, C. R., Rovers, M. M., de Vries, R. B. M., Leenaars, M., Ritskes-Hoitinga, M., & Langendam, M. W. (2014). SYRCLE’s risk of bias tool for animal studies. BMC Medical Research Methodology, 14, 43. https://doi.org/10.1186/1471-2288-14-43.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Bax, L., Yu, L. M., Ikeda, N., Tsuruta, H., & Moons, K. G. M. (2006). Development and validation of MIX: comprehensive free software for meta-analysis of causal research data. BMC Medical Research Methodology, 6, 50. https://doi.org/10.1186/1471-2288-6-50.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Smeda, M., Przyborowski, K., Proniewski, B., Zakrzewska, A., Kaczor, D., Stojak, M., Buczek, E., Nieckarz, Z., Zoladz, J. A., Wietrzyk, J., & Chlopicki, S. (2017). Breast cancer pulmonary metastasis is increased in mice undertaking spontaneous physical training in the running wheel; a call for revising beneficial effects of exercise on cancer progression. American Journal of Cancer Research, 7, 1926–1936.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. MacNeil, B., & Hoffman-Goetz, L. (1993). Exercise training and tumour metastasis in mice: influence of time of exercise onset. Anticancer Research, 13, 2085–2088.

    CAS  PubMed  Google Scholar 

  25. Hoffmann-Goetz, L., MacNeil, B., & Arumugam, Y. (1994). Tissue distribution of radiolabelled tumor cells in wheel exercised and sedentary mice. International Journal of Sports Medicine, 15, 249–253.

    Article  CAS  Google Scholar 

  26. Jadeski, L., & Hoffman-Goetz, L. (1996). Exercise and in vivo natural cytotoxicity against tumour cells of varying metastatic capacity. Clinical & Experimental Metastasis, 14, 138–144.

    Article  CAS  Google Scholar 

  27. Jee, H., Chang, J. E., & Yang, E. J. (2016). Positive prehabilitative effect of intense treadmill exercise for ameliorating cancer cachexia symptoms in a mouse model. Journal of Cancer, 7, 2378–2387. https://doi.org/10.7150/jca.17162.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Tsai, M. S., Kuo, M. L., Chang, C. C., & Wu, Y. T. (2013). The effects of exercise training on levels of vascular endothelial growth factor in tumor-bearing mice. Cancer Biomarkers, 13, 307–313. https://doi.org/10.3233/CBM-130359.

    Article  CAS  PubMed  Google Scholar 

  29. Uhlenbruck, G., & Order, U. (1991). Can endurance sports stimulate immune mechanisms against cancer and metastasis? International Journal of Sports Medicine, 12(Suppl 1), S63–S68. https://doi.org/10.1055/s-2007-1024753.

    Article  PubMed  Google Scholar 

  30. MacNeil, B., & Hoffman-Goetz, L. (1993). Effect of exercise on natural cytotoxicity and pulmonary tumor metastases in mice. Medicine & Science in Sports & Exercise, 25, 922–928.

    Article  CAS  Google Scholar 

  31. Murphy, E. A., Davis, J. M., Brown, A. S., Carmichael, M. D., Mayer, E. P., & Ghaffar, A. (2004). Effects of moderate exercise and oat beta-glucan on lung tumor metastases and macrophage antitumor cytotoxicity. Journal of Applied Physiology, 97, 955–959. https://doi.org/10.1152/japplphysiol.00252.2004.

    Article  CAS  PubMed  Google Scholar 

  32. Pedersen, L., Idorn, M., Olofsson, G. H., Lauenborg, B., Nookaew, I., Hansen, R. H., Johannesen, H. H., Becker, J. C., Pedersen, K. S., Dethlefsen, C., Nielsen, J., Gehl, J., Pedersen, B. K., Thor Straten, P., & Hojman, P. (2016). Voluntary running suppresses tumor growth through epinephrine- and IL-6-dependent NK cell mobilization and redistribution. Cell Metabolism, 23, 554–562. https://doi.org/10.1016/j.cmet.2016.01.011.

    Article  CAS  PubMed  Google Scholar 

  33. Alvarado, A., Gil da Costa, R. M., Faustino-Rocha, A. I., Ferreira, R., Lopes, C., Oliveira, P. A., & Colaço, B. (2017). Effects of exercise training on breast cancer metastasis in a rat model. International Journal of Experimental Pathology, 98, 40–46. https://doi.org/10.1111/iep.12225.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Hoffman-Goetz, L., May, K. M., & Arumugam, Y. (1994). Exercise training and mouse mammary tumour metastasis. Anticancer Research, 14, 2627–2631.

    CAS  PubMed  Google Scholar 

  35. Higgins, K. A., Park, D., Lee, G. Y., Curran, W. J., & Deng, X. (2014). Exercise-induced lung cancer regression: mechanistic findings from a mouse model. Cancer, 120, 3302–3310. https://doi.org/10.1002/cncr.28878.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Assi, M., Kenawi, M., Ropars, M., & Rébillard, A. (2017). Interleukin-6, C/EBP-β and PPAR-γ expression correlates with intramuscular liposarcoma growth in mice: the impact of voluntary physical activity levels. Biochemical and Biophysical Research Communications, 490, 1026–1032. https://doi.org/10.1016/j.bbrc.2017.06.158.

    Article  CAS  PubMed  Google Scholar 

  37. Zhang, Q. B., Zhang, B. H., Zhang, K. Z., Meng, X. T., Jia, Q. A., Zhang, Q. B., Bu, Y., Zhu, X. D., Ma, D. N., Ye, B. G., Zhang, N., Ren, Z. G., Sun, H. C., & Tang, Z. Y. (2016). Moderate swimming suppressed the growth and metastasis of the transplanted liver cancer in mice model: with reference to nervous system. Oncogene, 35, 4122–4131. https://doi.org/10.1038/onc.2015.484.

    Article  CAS  PubMed  Google Scholar 

  38. Zhang, Q. B., Meng, X. T., Jia, Q. A., Bu, Y., Ren, Z. G., Zhang, B. H., & Tang, Z. Y. (2016). Herbal compound songyou yin and moderate swimming suppress growth and metastasis of liver cancer by enhancing immune function. Integrative Cancer Therapies, 15, 368–375. https://doi.org/10.1177/1534735415622011.

    Article  CAS  PubMed  Google Scholar 

  39. Wolff, G., Davidson, S. J., Wrobel, J. K., & Toborek, M. (2015). Exercise maintains blood-brain barrier integrity during early stages of brain metastasis formation. Biochemical and Biophysical Research Communications, 463, 811–817. https://doi.org/10.1016/j.bbrc.2015.04.153.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Hoffman-Goetz, L., MacNeil, B., Arumugam, Y., & Randall Simpson, J. (1992). Differential effects of exercise and housing condition on murine natural killer cell activity and tumor growth. International Journal of Sports Medicine, 13, 167–171. https://doi.org/10.1055/s-2007-1021250.

    Article  CAS  PubMed  Google Scholar 

  41. Colbert, L. H., Westerlind, K. C., Perkins, S. N., Haines, D. C., Berrigan, D., Donehower, L. A., Fuchs-Young, R., & Hursting, S. D. (2009). Exercise effects on tumorigenesis in a p53-deficient mouse model of breast cancer. Medicine & Science in Sports & Exercise, 41, 1597–1605. https://doi.org/10.1249/MSS.0b013e31819f1f05.

    Article  CAS  Google Scholar 

  42. Bryner, R., Riggs, D., Donley, D., White, J., Ullrich, I., Lamm, D., et al. (1998). Effects of voluntary running wheel exercise on the growth and metastasis of transplanted prostate cancer in rats. Journal of Exercise Physiology Online, 1, 1–9.

    Google Scholar 

  43. Yan, L., & Demars, L. C. (2011). Effects of non-motorized voluntary running on experimental and spontaneous metastasis in mice. Anticancer Research, 31, 3337–3344.

    CAS  PubMed  Google Scholar 

  44. Davis, J. M., Kohut, M. L., Jackson, D. A., Colbert, L. H., Mayer, E. P., & Ghaffar, A. (1998). Exercise effects on lung tumor metastases and in vitro alveolar macrophage antitumor cytotoxicity. American Journal of Physiology, 274, R1454–R1459. https://doi.org/10.1152/ajpregu.1998.274.5.R1454.

    Article  CAS  PubMed  Google Scholar 

  45. MacNeil, B., & Hoffman-Goetz, L. (1993). Chronic exercise enhances in vivo and in vitro cytotoxic mechanisms of natural immunity in mice. Journal of Applied Physiology, 74, 388–395. https://doi.org/10.1152/jappl.1993.74.1.388.

    Article  CAS  PubMed  Google Scholar 

  46. Khori, V., Amani Shalamzari, S., Isanejad, A., Alizadeh, A. M., Alizadeh, S., Khodayari, S., Khodayari, H., Shahbazi, S., Zahedi, A., Sohanaki, H., Khaniki, M., Mahdian, R., Saffari, M., & Fayad, R. (2015). Effects of exercise training together with tamoxifen in reducing mammary tumor burden in mice: possible underlying pathway of miR-21. European Journal of Pharmacology, 765, 179–187. https://doi.org/10.1016/j.ejphar.2015.08.031.

    Article  CAS  PubMed  Google Scholar 

  47. Jones, L. W., Antonelli, J., Masko, E. M., Broadwater, G., Lascola, C. D., Fels, D., Dewhirst, M. W., Dyck, J. R., Nagendran, J., Flores, C. T., Betof, A. S., Nelson, E. R., Pollak, M., Dash, R. C., Young, M. E., & Freedland, S. J. (2012). Exercise modulation of the host-tumor interaction in an orthotopic model of murine prostate cancer. Journal of Applied Physiology, 113, 263–272. https://doi.org/10.1152/japplphysiol.01575.2011.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Garzia, L., Kijima, N., Morrissy, A. S., De Antonellis, P., Guerreiro-Stucklin, A., Holgado, B. L., et al. (2018). A hematogenous route for medulloblastoma leptomeningeal metastases. Cell, 172, 1050–1062.e14. https://doi.org/10.1016/j.cell.2018.01.038.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. McTiernan, A. (2008). Mechanisms linking physical activity with cancer. Nature Reviews Cancer, 8, 205–211. https://doi.org/10.1038/nrc2325.

    Article  CAS  PubMed  Google Scholar 

  50. Theriau, C. F., Shpilberg, Y., Riddell, M. C., & Connor, M. K. (2016). Voluntary physical activity abolishes the proliferative tumor growth microenvironment created by adipose tissue in animals fed a high fat diet. Journal of Applied Physiology, 121, 139–153. https://doi.org/10.1152/japplphysiol.00862.2015.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Bianco, T. M., Abdalla, D. R., Desidério, C. S., Thys, S., Simoens, C., Bogers, J. P., Murta, E. F. C., & Michelin, M. A. (2017). The influence of physical activity in the anti-tumor immune response in experimental breast tumor. Immunology Letters, 190, 148–158. https://doi.org/10.1016/j.imlet.2017.08.007.

    Article  CAS  PubMed  Google Scholar 

  52. Koelwyn, G. J., Quail, D. F., Zhang, X., White, R. M., & Jones, L. W. (2017). Exercise-dependent regulation of the tumour microenvironment. Nature Reviews Cancer, 17, 620–632. https://doi.org/10.1038/nrc.2017.78.

    Article  CAS  PubMed  Google Scholar 

  53. Jones, L. W., Fels, D. R., West, M., Allen, J. D., Broadwater, G., Barry, W. T., Wilke, L. G., Masko, E., Douglas, P. S., Dash, R. C., Povsic, T. J., Peppercorn, J., Marcom, P. K., Blackwell, K. L., Kimmick, G., Turkington, T. G., & Dewhirst, M. W. (2013). Modulation of circulating angiogenic factors and tumor biology by aerobic training in breast cancer patients receiving neoadjuvant chemotherapy. Cancer Prevention Research, 6, 925–937. https://doi.org/10.1158/1940-6207.CAPR-12-0416.

    Article  CAS  PubMed  Google Scholar 

  54. Pearson, M. J., & Smart, N. A. (2017). Aerobic training intensity for improved endothelial function in heart failure patients: a systematic review and meta-analysis. Cardiology Research and Practice, 2017, 2450202. https://doi.org/10.1155/2017/2450202.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Hojman, P., Gehl, J., Christensen, J. F., & Pedersen, B. K. (2018). Molecular mechanisms linking exercise to cancer prevention and treatment. Cell Metabolism, 27, 10–21. https://doi.org/10.1016/j.cmet.2017.09.015.

    Article  CAS  PubMed  Google Scholar 

  56. Goetz, J. G. (2018). Metastases go with the flow. Science, 362, 999–1000. https://doi.org/10.1126/science.aat9100.

    Article  CAS  PubMed  Google Scholar 

  57. Shachar, S. S., Williams, G. R., Muss, H. B., & Nishijima, T. F. (2016). Prognostic value of sarcopenia in adults with solid tumours: a meta-analysis and systematic review. European Journal of Cancer, 57, 58–67. https://doi.org/10.1016/j.ejca.2015.12.030.

    Article  PubMed  Google Scholar 

  58. Wolin, K. Y., Ruiz, J. R., Tuchman, H., & Lucia, A. (2010). Exercise in adult and pediatric hematological cancer survivors: an intervention review. Leukemia, 24, 1113–1120. https://doi.org/10.1038/leu.2010.54.

    Article  CAS  PubMed  Google Scholar 

  59. Pei, Y., Moore, C. E., Wang, J., Tewari, A. K., Eroshkin, A., Cho, Y. J., Witt, H., Korshunov, A., Read, T. A., Sun, J. L., Schmitt, E. M., Miller, C. R., Buckley, A. F., McLendon, R., Westbrook, T. F., Northcott, P. A., Taylor, M. D., Pfister, S. M., Febbo, P. G., & Wechsler-Reya, R. J. (2012). An animal model of MYC-driven medulloblastoma. Cancer Cell, 21, 155–167. https://doi.org/10.1016/j.ccr.2011.12.021.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Weiss, W. A., Aldape, K., Mohapatra, G., Feuerstein, B. G., & Bishop, J. M. (1997). Targeted expression of MYCN causes neuroblastoma in transgenic mice. EMBO Journal, 16, 2985–2995. https://doi.org/10.1093/emboj/16.11.2985.

    Article  CAS  PubMed  Google Scholar 

  61. Sweet-Cordero, E. A., & Biegel, J. A. (2019). The genomic landscape of pediatric cancers: implications for diagnosis and treatment. Science, 363, 1170–1175. https://doi.org/10.1126/science.aaw3535.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

Research by the authors is supported by the Spanish Ministry of Education, Culture and Sport [Javier S. Morales, contract #FPU14/03435, and Cecilia Rincón-Castanedo, contract #FPU16/03956]; Universidad de Alcalá [Pedro L. Valenzuela, contract #FPI2016]; the Spanish Ministry of Economy and Competitiveness and Fondos Feder [Alejandro Lucia, grant #PI15/00558 and PI18/00139]; the Spanish Ministry of Economy and Competitiveness [Miguel Servet research contract (Carmen Fiuza-Luces, ref. #CP18/00034)]; ‘Fundación Unoentrecienmil’; ‘Fundación MAPFRE’ [Convocatoria Ignacio H. de Larramendi]; and National Strength and Conditioning Association (NCSA) Foundation.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Carmen Fiuza-Luces.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(PDF 22 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rincón-Castanedo, C., Morales, J.S., Martín-Ruiz, A. et al. Physical exercise effects on metastasis: a systematic review and meta-analysis in animal cancer models. Cancer Metastasis Rev 39, 91–114 (2020). https://doi.org/10.1007/s10555-020-09851-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10555-020-09851-4

Keywords

Navigation