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Published in: Breast Cancer Research and Treatment 3/2016

01-10-2016 | Preclinical Study

Exercise regulates breast cancer cell viability: systemic training adaptations versus acute exercise responses

Authors: Christine Dethlefsen, Christian Lillelund, Julie Midtgaard, Christina Andersen, Bente Klarlund Pedersen, Jesper Frank Christensen, Pernille Hojman

Published in: Breast Cancer Research and Treatment | Issue 3/2016

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Abstract

Purpose

Exercise decreases breast cancer risk and disease recurrence, but the underlying mechanisms are unknown. Training adaptations in systemic factors have been suggested as mediating causes. We aimed to examine if systemic adaptations to training over time, or acute exercise responses, in breast cancer survivors could regulate breast cancer cell viability in vitro.

Methods

Blood samples were collected from breast cancer survivors, partaking in either a 6-month training intervention or across a 2 h acute exercise session. Changes in training parameters and systemic factors were evaluated and pre/post exercise-conditioned sera from both studies were used to stimulate breast cancer cell lines (MCF-7, MDA-MB-231) in vitro.

Results

Six months of training increased VO2peak (16.4 %, p < 0.001) and muscle strength, and reduced resting levels of plasma cholesterol (−18.2 %, p = 0.003) and cytokines. Yet, these systemic adaptations had no effect on breast cancer cell viability in vitro. During 2 h of acute exercise, increases in serum lactate (6-fold, p < 0.001), epinephrine (2.9-fold, p = 0.009), norepinephrine (2.2-fold, p < 0.001), and cytokines, including IL-6 (2.1-fold, p < 0.001) were detected. Incubation with serum obtained after exercise reduced viability by −9.2 % in MCF-7 (p = 0.04) and −9.4 % in MDA-MB-231 (p < 0.001) compared to resting serum.

Conclusion

Systemic changes to a 2 h exercise session reduced breast cancer viability, while adaptations to 6 months of training had no impact. Our data question the prevailing dogma that training-dependent baseline reductions in risk factors mediate the protective effect of exercise on breast cancer. Instead, we propose that the cancer protection is driven by accumulative effects of repeated acute exercise responses.
Literature
1.
go back to reference Dirx MJ, Voorrips LE, Goldbohm RA et al (2001) Baseline recreational physical activity, history of sports participation, and postmenopausal breast carcinoma risk in the Netherlands Cohort Study. Cancer 92:1638–1649CrossRefPubMed Dirx MJ, Voorrips LE, Goldbohm RA et al (2001) Baseline recreational physical activity, history of sports participation, and postmenopausal breast carcinoma risk in the Netherlands Cohort Study. Cancer 92:1638–1649CrossRefPubMed
2.
go back to reference Fraser GE, Shavlik D (1997) Risk factors, lifetime risk, and age at onset of breast cancer. Ann Epidemiol 7:375–382CrossRefPubMed Fraser GE, Shavlik D (1997) Risk factors, lifetime risk, and age at onset of breast cancer. Ann Epidemiol 7:375–382CrossRefPubMed
3.
go back to reference Lahmann PH, Friedenreich C, Schuit AJ et al (2007) Physical activity and breast cancer risk: the European Prospective Investigation into cancer and nutrition. Cancer Epidemiol Biomarkers Prev 16:36–42CrossRefPubMed Lahmann PH, Friedenreich C, Schuit AJ et al (2007) Physical activity and breast cancer risk: the European Prospective Investigation into cancer and nutrition. Cancer Epidemiol Biomarkers Prev 16:36–42CrossRefPubMed
4.
go back to reference McTiernan A, Kooperberg C, White E et al (2003) Recreational physical activity and the risk of breast cancer in postmenopausal women: the Women’s Health Initiative Cohort Study. JAMA 290:1331–1336CrossRefPubMed McTiernan A, Kooperberg C, White E et al (2003) Recreational physical activity and the risk of breast cancer in postmenopausal women: the Women’s Health Initiative Cohort Study. JAMA 290:1331–1336CrossRefPubMed
5.
go back to reference Patel AV, Callel EE, Bernstein L et al (2003) Recreational physical activity and risk of postmenopausal breast cancer in a large cohort of US women. Cancer Causes Control 14:519–529CrossRefPubMed Patel AV, Callel EE, Bernstein L et al (2003) Recreational physical activity and risk of postmenopausal breast cancer in a large cohort of US women. Cancer Causes Control 14:519–529CrossRefPubMed
6.
go back to reference Rockhill B, Willett WC, Hunter DJ et al (1999) A prospective study of recreational physical activity and breast cancer risk. Arch Intern Med 159:2290–2296CrossRefPubMed Rockhill B, Willett WC, Hunter DJ et al (1999) A prospective study of recreational physical activity and breast cancer risk. Arch Intern Med 159:2290–2296CrossRefPubMed
7.
go back to reference Tehard B, Friedenreich CM, Oppert JM et al (2006) Effect of physical activity on women at increased risk of breast cancer: results from the E3N cohort study. Cancer Epidemiol Biomarkers Prev 15:57–64CrossRefPubMed Tehard B, Friedenreich CM, Oppert JM et al (2006) Effect of physical activity on women at increased risk of breast cancer: results from the E3N cohort study. Cancer Epidemiol Biomarkers Prev 15:57–64CrossRefPubMed
8.
go back to reference Thune I, Brenn T, Lund E et al (1997) Physical activity and the risk of breast cancer. N Engl J Med 336:1269–1275CrossRefPubMed Thune I, Brenn T, Lund E et al (1997) Physical activity and the risk of breast cancer. N Engl J Med 336:1269–1275CrossRefPubMed
9.
go back to reference Ballard-Barbash R, Friedenreich CM, Courneya KS et al (2012) Physical activity, biomarkers, and disease outcomes in cancer survivors: a systematic review. J Natl Cancer Inst 104:815–840CrossRefPubMedPubMedCentral Ballard-Barbash R, Friedenreich CM, Courneya KS et al (2012) Physical activity, biomarkers, and disease outcomes in cancer survivors: a systematic review. J Natl Cancer Inst 104:815–840CrossRefPubMedPubMedCentral
10.
11.
go back to reference Moore SC, Lee IM, Weiderpass E et al (2016) Association of leisure-time physical activity with risk of 26 types of cancer in 1.44 million adults. JAMA Intern Med 176:816–825CrossRefPubMed Moore SC, Lee IM, Weiderpass E et al (2016) Association of leisure-time physical activity with risk of 26 types of cancer in 1.44 million adults. JAMA Intern Med 176:816–825CrossRefPubMed
12.
go back to reference Beasley JM, Kwan ML, Chen WY et al (2012) Meeting the physical activity guidelines and survival after breast cancer: findings from the after breast cancer pooling project. Breast Cancer Res Treat 131:637–643CrossRefPubMed Beasley JM, Kwan ML, Chen WY et al (2012) Meeting the physical activity guidelines and survival after breast cancer: findings from the after breast cancer pooling project. Breast Cancer Res Treat 131:637–643CrossRefPubMed
13.
go back to reference Bradshaw PT, Ibrahim JG, Khankari N et al (2014) Post-diagnosis physical activity and survival after breast cancer diagnosis: the Long Island Breast Cancer Study. Breast Cancer Res Treat 145:735–742CrossRefPubMedPubMedCentral Bradshaw PT, Ibrahim JG, Khankari N et al (2014) Post-diagnosis physical activity and survival after breast cancer diagnosis: the Long Island Breast Cancer Study. Breast Cancer Res Treat 145:735–742CrossRefPubMedPubMedCentral
14.
go back to reference Chen X, Lu W, Zheng W et al (2011) Exercise after diagnosis of breast cancer in association with survival. Cancer Prev Res 4:1409–1418CrossRef Chen X, Lu W, Zheng W et al (2011) Exercise after diagnosis of breast cancer in association with survival. Cancer Prev Res 4:1409–1418CrossRef
15.
go back to reference Holick CN, Newcomb PA, Trentham-Dietz A et al (2008) Physical activity and survival after diagnosis of invasive breast cancer. Cancer Epidemiol Biomarkers Prev 17:379–386CrossRefPubMed Holick CN, Newcomb PA, Trentham-Dietz A et al (2008) Physical activity and survival after diagnosis of invasive breast cancer. Cancer Epidemiol Biomarkers Prev 17:379–386CrossRefPubMed
16.
go back to reference Holmes MD, Chen WY, Feskanich D et al (2005) Physical activity and survival after breast cancer diagnosis. JAMA 293:2479–2486CrossRefPubMed Holmes MD, Chen WY, Feskanich D et al (2005) Physical activity and survival after breast cancer diagnosis. JAMA 293:2479–2486CrossRefPubMed
17.
go back to reference Irwin ML, McTiernan A, Manson JE et al (2011) Physical activity and survival in postmenopausal women with breast cancer: results from the women’s health initiative. Cancer Prev Res 4:522–529CrossRef Irwin ML, McTiernan A, Manson JE et al (2011) Physical activity and survival in postmenopausal women with breast cancer: results from the women’s health initiative. Cancer Prev Res 4:522–529CrossRef
18.
go back to reference Williams PT (2014) Significantly greater reduction in breast cancer mortality from post-diagnosis running than walking. Int J Cancer 135:1195–1202CrossRefPubMed Williams PT (2014) Significantly greater reduction in breast cancer mortality from post-diagnosis running than walking. Int J Cancer 135:1195–1202CrossRefPubMed
19.
go back to reference Alfano CM, Bluethmann SM, Tesauro G et al (2016) NCI funding trends and priorities in physical activity and energy balance research among cancer survivors. J Natl Cancer Inst 108(1):djv285CrossRefPubMed Alfano CM, Bluethmann SM, Tesauro G et al (2016) NCI funding trends and priorities in physical activity and energy balance research among cancer survivors. J Natl Cancer Inst 108(1):djv285CrossRefPubMed
20.
21.
go back to reference Pedersen BK, Hoffman-Goetz L (2000) Exercise and the immune system: regulation, integration, and adaptation. Physiol Rev 80:1055–1081PubMed Pedersen BK, Hoffman-Goetz L (2000) Exercise and the immune system: regulation, integration, and adaptation. Physiol Rev 80:1055–1081PubMed
22.
go back to reference Pedersen BK, Steensberg A, Fischer C et al (2001) Exercise and cytokines with particular focus on muscle-derived IL-6. Exerc Immunol Rev 7:18–31PubMed Pedersen BK, Steensberg A, Fischer C et al (2001) Exercise and cytokines with particular focus on muscle-derived IL-6. Exerc Immunol Rev 7:18–31PubMed
23.
go back to reference Zouhal H, Jacob C, Delamarche P et al (2008) Catecholamines and the effects of exercise, training and gender. Sports Med 38:401–423CrossRefPubMed Zouhal H, Jacob C, Delamarche P et al (2008) Catecholamines and the effects of exercise, training and gender. Sports Med 38:401–423CrossRefPubMed
24.
go back to reference Midtgaard J, Christensen JF, Tolver A et al (2013) Efficacy of multimodal exercise-based rehabilitation on physical activity, cardiorespiratory fitness, and patient-reported outcomes in cancer survivors: a randomized, controlled trial. Ann Oncol 24:2267–2273CrossRefPubMedPubMedCentral Midtgaard J, Christensen JF, Tolver A et al (2013) Efficacy of multimodal exercise-based rehabilitation on physical activity, cardiorespiratory fitness, and patient-reported outcomes in cancer survivors: a randomized, controlled trial. Ann Oncol 24:2267–2273CrossRefPubMedPubMedCentral
25.
go back to reference Adamsen L, Quist M, Andersen C et al (2009) Effect of a multimodal high intensity exercise intervention in cancer patients undergoing chemotherapy: randomised controlled trial. BMJ 339:b3410CrossRefPubMedPubMedCentral Adamsen L, Quist M, Andersen C et al (2009) Effect of a multimodal high intensity exercise intervention in cancer patients undergoing chemotherapy: randomised controlled trial. BMJ 339:b3410CrossRefPubMedPubMedCentral
26.
go back to reference Midtgaard J (2013) Theoretical and practical outline of the Copenhagen PACT narrative-based exercise counselling manual to promote physical activity in post-therapy cancer survivors. Acta Oncol 52:303–309CrossRefPubMed Midtgaard J (2013) Theoretical and practical outline of the Copenhagen PACT narrative-based exercise counselling manual to promote physical activity in post-therapy cancer survivors. Acta Oncol 52:303–309CrossRefPubMed
27.
go back to reference Durnin JV, Womersley J (1974) Body fat assessed from total body density and its estimation from skinfold thickness: measurements on 481 men and women aged from 16 to 72 years. Br J Nutr 32:77–97CrossRefPubMed Durnin JV, Womersley J (1974) Body fat assessed from total body density and its estimation from skinfold thickness: measurements on 481 men and women aged from 16 to 72 years. Br J Nutr 32:77–97CrossRefPubMed
28.
go back to reference Niles AL, Moravec RA, Eric Hesselberth P et al (2007) A homogeneous assay to measure live and dead cells in the same sample by detecting different protease markers. Anal Biochem 366:197–206CrossRefPubMed Niles AL, Moravec RA, Eric Hesselberth P et al (2007) A homogeneous assay to measure live and dead cells in the same sample by detecting different protease markers. Anal Biochem 366:197–206CrossRefPubMed
29.
go back to reference Rogers LQ, Courneya KS, Anton PM et al (2015) Effects of the BEAT cancer physical activity behavior change intervention on physical activity, aerobic fitness, and quality of life in breast cancer survivors: a multicenter randomized controlled trial. Breast Cancer Res Treat 149:109–119CrossRefPubMed Rogers LQ, Courneya KS, Anton PM et al (2015) Effects of the BEAT cancer physical activity behavior change intervention on physical activity, aerobic fitness, and quality of life in breast cancer survivors: a multicenter randomized controlled trial. Breast Cancer Res Treat 149:109–119CrossRefPubMed
30.
go back to reference Winters-Stone KM, Dobek J, Bennett JA et al (2012) The effect of resistance training on muscle strength and physical function in older, postmenopausal breast cancer survivors: a randomized controlled trial. J Cancer Surviv 6:189–199CrossRefPubMed Winters-Stone KM, Dobek J, Bennett JA et al (2012) The effect of resistance training on muscle strength and physical function in older, postmenopausal breast cancer survivors: a randomized controlled trial. J Cancer Surviv 6:189–199CrossRefPubMed
31.
go back to reference Schmitz KH, Williams NI, Kontos D et al (2015) Dose-response effects of aerobic exercise on estrogen among women at high risk for breast cancer: a randomized controlled trial. Breast Cancer Res Treat 154:309–318CrossRefPubMed Schmitz KH, Williams NI, Kontos D et al (2015) Dose-response effects of aerobic exercise on estrogen among women at high risk for breast cancer: a randomized controlled trial. Breast Cancer Res Treat 154:309–318CrossRefPubMed
32.
go back to reference Smith AJ, Phipps WR, Thomas W et al (2013) The effects of aerobic exercise on estrogen metabolism in healthy premenopausal women. Cancer Epidemiol Biomarkers Prev 22:756–764CrossRefPubMedPubMedCentral Smith AJ, Phipps WR, Thomas W et al (2013) The effects of aerobic exercise on estrogen metabolism in healthy premenopausal women. Cancer Epidemiol Biomarkers Prev 22:756–764CrossRefPubMedPubMedCentral
33.
go back to reference Campbell KL, Westerlind KC, Harber VJ et al (2007) Effects of aerobic exercise training on estrogen metabolism in premenopausal women: a randomized controlled trial. Cancer Epidemiol Biomarkers Prev 16:731–739CrossRefPubMed Campbell KL, Westerlind KC, Harber VJ et al (2007) Effects of aerobic exercise training on estrogen metabolism in premenopausal women: a randomized controlled trial. Cancer Epidemiol Biomarkers Prev 16:731–739CrossRefPubMed
34.
go back to reference McTiernan A, Tworoger SS, Ulrich CM et al (2004) Effect of exercise on serum estrogens in postmenopausal women: a 12-month randomized clinical trial. Cancer Res 64:2923–2928CrossRefPubMed McTiernan A, Tworoger SS, Ulrich CM et al (2004) Effect of exercise on serum estrogens in postmenopausal women: a 12-month randomized clinical trial. Cancer Res 64:2923–2928CrossRefPubMed
35.
go back to reference Moore SC, Lee IM, Weiderpass E et al (2016) Association of leisure-time physical activity with risk of 26 types of cancer in 144 million adults. JAMA Intern Med 176:816–825CrossRefPubMed Moore SC, Lee IM, Weiderpass E et al (2016) Association of leisure-time physical activity with risk of 26 types of cancer in 144 million adults. JAMA Intern Med 176:816–825CrossRefPubMed
36.
go back to reference Aoi W, Naito Y, Takagi T et al (2013) A novel myokine, secreted protein acidic and rich in cysteine (SPARC), suppresses colon tumorigenesis via regular exercise. Gut 62:882–889CrossRefPubMed Aoi W, Naito Y, Takagi T et al (2013) A novel myokine, secreted protein acidic and rich in cysteine (SPARC), suppresses colon tumorigenesis via regular exercise. Gut 62:882–889CrossRefPubMed
37.
go back to reference Hojman P, Dethlefsen C, Brandt C et al (2011) Exercise-induced muscle-derived cytokines inhibit mammary cancer cell growth. Am J Physiol Endocrinol Metab 301:E504–E510CrossRefPubMed Hojman P, Dethlefsen C, Brandt C et al (2011) Exercise-induced muscle-derived cytokines inhibit mammary cancer cell growth. Am J Physiol Endocrinol Metab 301:E504–E510CrossRefPubMed
39.
go back to reference Henningsen J (2010) Dynamics of the skeletal muscle secretome during myoblast differentiation. Mol Cell Proteom 9(11):2482–2496CrossRef Henningsen J (2010) Dynamics of the skeletal muscle secretome during myoblast differentiation. Mol Cell Proteom 9(11):2482–2496CrossRef
Metadata
Title
Exercise regulates breast cancer cell viability: systemic training adaptations versus acute exercise responses
Authors
Christine Dethlefsen
Christian Lillelund
Julie Midtgaard
Christina Andersen
Bente Klarlund Pedersen
Jesper Frank Christensen
Pernille Hojman
Publication date
01-10-2016
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 3/2016
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-016-3970-1

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