The Regulation of the Metastatic Cascade by Physical Activity: A Narrative Review

Ryen, Sophie van Doorslaer de ten; Deldicque, Louise

doi:10.3390/cancers12010153

Cited by 13 publications

(11 citation statements)

References 54 publications

(98 reference statements)

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“…Together this indicates that tumor progression could be slowed or prevented by physical activity and indeed physical activity regulates multiple steps of the metastatic cascade, as comprehensively reviewed in [247]. In summary, moderate intensity exercise appears to prevent tumor spread by normalizing angiogenesis, reducing circulating tumor cells and decreasing endothelial cell permeability [247][248][249]. On the contrary, high-intensity exercise may favor cancer dissemination and promote the formation of the premetastatic niche through excessive stress [247,250].…”

Section: Targeting Metastasis Via the Treatment Of Obesitymentioning

confidence: 98%

“…In summary, moderate intensity exercise appears to prevent tumor spread by normalizing angiogenesis, reducing circulating tumor cells and decreasing endothelial cell permeability [247][248][249]. On the contrary, high-intensity exercise may favor cancer dissemination and promote the formation of the premetastatic niche through excessive stress [247,250]. In overweight or obese breast cancer survivors, moderate to vigorous exercise three times a week for 16 weeks reduced systemic levels of insulin, IGF-1 and leptin, and increased adiponectin [251].…”

Section: Targeting Metastasis Via the Treatment Of Obesitymentioning

confidence: 98%

“…In contrast, a decreased physical activity level between pre-to post-diagnosis is associated with higher cancer mortality [246]. Together this indicates that tumor progression could be slowed or prevented by physical activity and indeed physical activity regulates multiple steps of the metastatic cascade, as comprehensively reviewed in [247]. In summary, moderate intensity exercise appears to prevent tumor spread by normalizing angiogenesis, reducing circulating tumor cells and decreasing endothelial cell permeability [247][248][249].…”

Section: Targeting Metastasis Via the Treatment Of Obesitymentioning

confidence: 99%

“…In overweight or obese breast cancer survivors, moderate to vigorous exercise three times a week for 16 weeks reduced systemic levels of insulin, IGF-1 and leptin, and increased adiponectin [251]. Therefore, chronic adaptations to moderate-intensity endurance exercise may be the most effective way to achieve a preventive effect of exercise on metastases [247]. Overall, exercise and nutritional strategies may be especially beneficial in overweight or obese cancer survivors to reduce both obesity-associated comorbidities and prevent cancer reoccurrence.…”

Section: Targeting Metastasis Via the Treatment Of Obesitymentioning

confidence: 99%

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Obesity and Cancer Metastasis: Molecular and Translational Perspectives

Annett

Moore

Robson

2020

Cancers

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Obesity is a modern health problem that has reached pandemic proportions. It is an established risk factor for carcinogenesis, however, evidence for the contribution of adipose tissue to the metastatic behavior of tumors is also mounting. Over 90% of cancer mortality is attributed to metastasis and metastatic tumor cells must communicate with their microenvironment for survival. Many of the characteristics observed in obese adipose tissue strongly mirror the tumor microenvironment. Thus in the case of prostate, pancreatic and breast cancer and esophageal adenocarcinoma, which are all located in close anatomical proximity to an adipose tissue depot, the adjacent fat provides an ideal microenvironment to enhance tumor growth, progression and metastasis. Adipocytes provide adipokines, fatty acids and other soluble factors to tumor cells whilst immune cells infiltrate the tumor microenvironment. In addition, there are emerging studies on the role of the extracellular vesicles secreted from adipose tissue, and the extracellular matrix itself, as drivers of obesity-induced metastasis. In the present review, we discuss the major mechanisms responsible for the obesity–metastatic link. Furthermore, understanding these complex mechanisms will provide novel therapies to halt the tumor–adipose tissue crosstalk with the ultimate aim of inhibiting tumor progression and metastatic growth.

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Section: Targeting Metastasis Via the Treatment Of Obesitymentioning

confidence: 98%

Section: Targeting Metastasis Via the Treatment Of Obesitymentioning

confidence: 98%

Section: Targeting Metastasis Via the Treatment Of Obesitymentioning

confidence: 99%

Section: Targeting Metastasis Via the Treatment Of Obesitymentioning

confidence: 99%

See 2 more Smart Citations

Obesity and Cancer Metastasis: Molecular and Translational Perspectives

Annett

Moore

Robson

2020

Cancers

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show abstract

“…On the contrary, many rodent models of exercise fail to show an effect on tumor growth and/or survival if the exercise regimen is first initiated after tumor inoculation [35][36][37][38]. To this end, MacNeil and colleagues [37] observed that exercise prior to tumor inoculation decreased metastasis as discussed above, whereas exercise after tumor inoculation did little on its own.…”

Section: Preclinical Data From Rodent Animal Models Of Cancer and Exercisementioning

confidence: 99%

Exercise Oncology and Immuno-Oncology; A (Future) Dynamic Duo

Olofsson

Jensen

Idorn

et al. 2020

IJMS

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Recent advances in clinical oncology is based on exploiting the capacity of the immune system to combat cancer: immuno-oncology. Thus, immunotherapy of cancer is now used to treat a variety of malignant diseases. A striking feature is that even patients with late-stage disease may experience curative responses. However, most patients still succumb to disease, and do not benefit from treatment. Exercise has gained attention in clinical oncology and has been used for many years to improve quality of life, as well as to counteract chemotherapy-related complications. However, more recently, exercise has garnered interest, largely due to data from animal studies suggesting a striking therapeutic effect in preclinical cancer models; an effect largely mediated by the immune system. In humans, physical activity is associated with a lower risk for a variety of malignancies, and some data suggest a positive clinical effect for cancer patients. Exercise leads to mobilization of cells of the immune system, resulting in redistribution to different body compartments, and in preclinical models, exercise has been shown to lead to immunological changes in the tumor microenvironment. This suggests that exercise and immunotherapy could have a synergistic effect if combined.

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Voluntary exercise influences metastatic organotropism in a murine colorectal cancer model

Wijler

Raats

Verheem

et al. 2021

JCSM Rapid Communications

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Background Physical activity is associated with a lower risk of colorectal cancer (CRC) and CRC-specific mortality. However, evidence for a causal relationship between physical activity and disease progression is lacking. Here, we have used CRC organoids to create a novel mouse model for spontaneous metastasis formation to multiple organs. We have used this model to assess the influence of voluntary exercise on disease progression. Methods Collagen-embedded murine colorectal tumour organoids were transplanted into the livers of immunocompetent C57Bl/6 mice using microsurgery. Voluntary exercise in tumour-bearing mice was modelled by offering running wheels continuously (n = 12) or 3 h/day (n = 12) versus no wheel access (n = 12). Running wheel revolutions were cumulatively measured every 30 min and physical activity was continuously monitored by infrared cameras. Food intake was monitored throughout the experiment and body composition was assessed with echoMRI. Animals were sacrificed 14 weeks after tumour initiation. Tumour load was quantified by EpCAM immunohistochemistry staining. Systemic inflammation parameters were assessed in blood plasma by a multiplex immunoassay. Results Tumour growth was initiated by implantation of CRC organoids into the livers of immunocompetent mice. The resulting tumours spontaneously formed distant metastases to non-implanted liver lobes and to the lungs. Mice with access to the running wheels for 3 h/day ran relatively short distances (2.3 ± 0.3 km/night; 221 ± 29 km total distance) with relatively high intensity (wheel revolutions/h). Mice with continuous access to the running wheels ran significantly longer distances (6.6 ± 3.0 km/night; 600 ± 290 km total distance) with a significantly lower intensity. Both exercise groups showed increased lean body mass, and decreased fat mass and body weight compared with tumour-bearing control mice. Food intake was unaffected by exercise or tumour growth. Primary tumour growth was not significantly affected by exercise. However, mice with continuous wheel access (long distance-lower intensity group) displayed increased lung metastasis and decreased liver metastasis formation, when compared with the sedentary control group. Short distance-higher intensity exercise did not affect metastasis formation. Analysis of blood cytokine levels revealed that mice with continuous wheel access displayed signs of systemic inflammation. Conclusions These results suggest that exercise has the potential to influence the patterns and extent of metastasis in CRC, and that the degree and intensity of exercise are likely to be important variables. Confirmation of these results in additional preclinical models with or without systemic treatment is warranted.

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The Regulation of the Metastatic Cascade by Physical Activity: A Narrative Review

Cited by 13 publications

References 54 publications

Obesity and Cancer Metastasis: Molecular and Translational Perspectives

Obesity and Cancer Metastasis: Molecular and Translational Perspectives

Exercise Oncology and Immuno-Oncology; A (Future) Dynamic Duo

Voluntary exercise influences metastatic organotropism in a murine colorectal cancer model

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