Voluntary exercise in mesothelioma: effects on tumour growth and treatment response in a murine model

Our plain-English summary of Voluntary exercise in mesothelioma: effects on tumour growth and treatment response in a murine model, by S.A. Fisher, C.J. Peddle-McIntyre, K. Burton, et al (BMC Research Notes, 2020).

The study

• Authors: S.A. Fisher, C.J. Peddle-McIntyre, K. Burton, R.U. Newton, E. Marcq, R.A. Lake, A.K. Nowak
• Journal: BMC Research Notes
• Published: 2020;13(1):435
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Objective: There is substantial evidence that exercise can safely reduce the risk of cancer and improve survival in different human cancer populations. Long latency periods associated with carcinogen-induced cancers like asbestos induced mesothelioma provide an opportunity to implement exercise as an intervention to delay or prevent disease development. However, there are limited studies investigating the ability of exercise to prevent or delay cancer, and exercise as a preventive strategy has never been assessed in models with a known carcinogen. We investigated the potential of voluntary exercise (VE) to delay development of asbestos related disease (ARD) in our well-characterised, asbestos induced MexTAg model of mesothelioma.

Results: Asbestos exposed MexTAg mice were given continuous or delayed access to VE and ARD assessed over time. We found that the addition of VE did not affect ARD development in asbestos exposed MexTAg mice. However, non-asbestos exposed, aged matched control mice participated in significantly more VE behaviours, suggesting subclinical development of ARD after asbestos exposure had a greater impact on VE participation than age alone. These data highlight the importance of model choice and the potential limitation that some pre-clinical studies may not accurately represent the clinical paradigm, particularly in the context of prevention studies.

In plain English

This was an experiment in mice, not people. The authors used MexTAg mice, a genetically modified mesothelioma model strain, in groups of 28 to 30. The mice received crocidolite asbestos as two 3 mg injections into the abdomen, four weeks apart. Some had active running wheels from 2 weeks before exposure, some from 25 weeks after, and some had only locked wheels. Age-matched mice not given asbestos served as comparisons. Wheel access made no significant difference to median survival: 39.9 weeks with early access and 44.9 weeks with later access, versus 45.3 weeks without an active wheel. Time to first signs of disease also did not differ. All unexposed mice survived to 70 weeks except one, culled at week 44 in an incident unrelated to exercise. Running declined more in asbestos-exposed mice (2.97 to 12.63-fold) than in unexposed mice (1.51 to 4.28-fold). The authors concluded that exercise did not significantly affect asbestos related disease in this model. They suggested that developing disease reduced exercise more than age alone did. They noted that three mice shared each cage, so running data were not per mouse.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal experiment in transgenic (MexTAg) mice, randomly assigned to groups with or without access to active running wheels
• Who was studied: MexTAg transgenic mice, male and female, 28 to 30 per group, aged 6 to 20 weeks. Asbestos-exposed groups were: active wheel access from 2 weeks before exposure (Pre-VE), active wheel access from 25 weeks after exposure (Post-VE), or no access to an active wheel (No VE). Age-matched non-asbestos-exposed controls were also studied: 'Young' (90 days at start of wheel access) and 'Old' (265 days). The study was done at the University of Western Australia.
• Exposure: Crocidolite asbestos was given as two 0.5 ml (3 mg) intraperitoneal injections per mouse at weeks 0 and 4 (6 mg total). The intervention was voluntary exercise on an activated running wheel, either continuous from 2 weeks before asbestos or starting 25 weeks after asbestos. Cages received an activated or a locked wheel.
• Main results:
  • Among asbestos-exposed mice, median survival did not differ significantly with active wheel access: Pre-VE 39.9 vs No VE 45.3 weeks (p = 0.2784); Post-VE 44.9 vs No VE 45.3 weeks (p = 0.7404).
  • Time from asbestos exposure to first signs of disease did not differ between asbestos-exposed groups: Pre-VE 39.3 weeks, Post-VE 42.9 weeks, No VE 43.1 weeks.
  • All but 3 asbestos-exposed mice (2 from No VE, 1 from Post-VE) died of asbestos related disease by 70 weeks. The text states that all age-matched non-asbestos-exposed controls survived to the 70-week endpoint, but the Figure 2 caption reports that one control mouse was culled at week 44 in an incident unrelated to exercise.
  • All asbestos-exposed mice ran progressively less over the 70 weeks. The decline was significant after 15 weeks of wheel access in both Pre-VE and Post-VE groups. In the Post-VE group, running was almost negligible for mice surviving to 70 weeks.
  • Unexposed control mice also ran significantly less over time (p < 0.01), but the decrease was smaller: 1.51 to 4.28-fold in non-asbestos groups vs 2.97 to 12.63-fold in asbestos-exposed groups.
  • Among unexposed controls, 'Old' controls (delayed wheel access) ran significantly more (p < 0.05) than 'Young' controls (continuous access).
• The authors' conclusion: The authors concluded that continuous or delayed voluntary exercise did not significantly affect asbestos related disease development in asbestos-exposed MexTAg mice. They suggested that disease developing before visible signs reduced exercise more than age alone did. They also suggested that exercise alone may not be enough to counteract strong carcinogens like asbestos, and that model choice matters.
• Limitations the authors state:
  • Three mice were housed per cage, so exercise data do not reflect individual mice.
  • Other, individualized forms of exercise might be more effective than the continuous voluntary wheel running used here.
  • Investigators could not be blinded to treatment groups.
  • The genetic modifications in the transgenic MexTAg model might mask any benefit of exercise.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Latency, Asbestos Exposure.

Related studies

• A commercially available preparation of Staphylococcus aureus bio-products potently inhibits tumour growth in a murine model of mesothelioma — S.M. Lansley, J.F. Varano Della Vergiliana, et al. (2014)
• Growth factor responses and protooncogene expression of murine mesothelial cell lines derived from asbestos-induced mesotheliomas — L.A. Goodglick, C.A. Vaslet, et al. (1997)
• Fractionated low-dose radiotherapy primes the tumor microenvironment for immunotherapy in a murine mesothelioma model — R.A. D'Alonzo, S. Keam, et al. (2025)
• Tretinoin improves the anti-cancer response to cyclophosphamide, in a model-selective manner — C.M. Tilsed, M.L.O. Morales, et al. (2024)
• Establishment of a murine model of malignant mesothelioma — M.R. Davis, L.S. Manning, et al. (1992)
• Gene expression profiles reveal increased mClca3 (Gob5) expression and mucin production in a murine model of asbestos-induced fibrogenesis — T. Sabo-Attwood, M. Ramos-Nino, et al. (2005)

Browse more research in BMC Research Notes, or return to medical research.