Opinion | Published:

Exercise-dependent regulation of the tumour microenvironment

Nature Reviews Cancer volume 17, pages 620632 (2017) | Download Citation

Abstract

The integrity and composition of the tumour microenvironment (TME) is highly plastic, undergoing constant remodelling in response to instructive signals derived from alterations in the availability and nature of systemic host factors. This 'systemic milieu' is directly modulated by host exposure to modifiable lifestyle factors such as exercise. Host exposure to regular exercise markedly reduces the risk of the primary development of several cancers and might improve clinical outcomes following a diagnosis of a primary disease. However, the molecular mechanisms that underpin the apparent antitumour effects of exercise are poorly understood. In this Opinion article, we explore the putative effects of exercise in reprogramming the interaction between the host and the TME. Specifically, we speculate on the possible effects of exercise on reprogramming 'distant' tissue microenvironments (those not directly involved in the exercise response) by analysing how alterations in the systemic milieu might modulate key TME components to influence cancer hallmarks.

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Acknowledgements

L.W.J. is supported by research grants from the National Cancer Institute, AKTIV Against Cancer and the Memorial Sloan Kettering Cancer Center Support Grant/Core Grant (P30 CA008748). The authors would like to thank N. Eves and anonymous reviewers for insights and feedback on earlier versions of this manuscript as well as W. Underwood for administrative support. The authors apologize to the many authors whose work we were unable to cite owing to space constraints.

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Affiliations

  1. Graeme J. Koelwyn is at the NYU Langone Medical Center, Marc and Ruti Bell Vascular Biology and Disease Program, Leon H. Charney Division of Cardiology, Department of Medicine, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA.

    • Graeme J. Koelwyn
  2. Daniela F. Quail is at the Goodman Cancer Research Centre, McGill University; and at the Department of Physiology, McGill University, 1160 Pine Avenue West, Montreal, Quebec H3A 1A3, Canada.

    • Daniela F. Quail
  3. Xiang Zhang is at the Lester and Sue Smith Breast Center, Baylor College of Medicine; and at the Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.

    • Xiang Zhang
  4. Richard M. White is at the Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.

    • Richard M. White
  5. Lee W. Jones is at the Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA; and at the Weil Cornell Medical Center, 1275 York Avenue, New York, New York 10065, USA.

    • Lee W. Jones

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Contributions

G.J.K., D.F.Q. and L.W.J. researched data for the article, made substantial contributions to the discussion of content and wrote the manuscript. All authors reviewed and edited the manuscript before submission. G.J.K. and D.F.Q. are joint first authors.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Lee W. Jones.

Glossary

Caloric restriction

Reduction in calorie consumption.

Cardiorespiratory fitness

The integrative capacity of the pulmonary and cardiovascular systems, the vasculature, blood and skeletal muscle to deliver and/or utilize oxygen from the environment to the skeletal muscle mitochondria.

Chronic exercise

Structured, repeated and purposeful physical activity with the objective of improving health or cardiorespiratory fitness.

Exercise prescription

A specific regimen with details regarding the frequency, duration, modality, intensity and length of exercise training.

Homeostasis

The need to maintain a stable internal environment in the face of pathological and physiological perturbations.

Homeostatic control circuits

Specialized homeostatic systems that operate at the cellular, tissue and systemic levels to regulate physiological processes within predefined ranges ('set points').

Pathological angiogenesis

Dysfunctional or non-productive angiogenesis that results in pathological phenotypes.

Physical activity

Any bodily movement produced by skeletal muscles that requires energy expenditure above resting levels.

Physiological angiogenesis

Functional or productive angiogenesis that results in physiological phenotypes.

Pre-metastatic niche

Secondary organ microenvironments (for example, lung, liver, brain or bone) that undergo molecular and possibly architectural alterations to augment engraftment and survival of subsequent tumour cell arrival.

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DOI

https://doi.org/10.1038/nrc.2017.78

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