Effects of 8‑Week Noncontinuous Aerobic Exercise on the Levels of CCL2, CCL5, and their Respective Receptors in Female BALB/C Mice Suffering from Breast Cancer

Mehrnoosh Esmailiyan, Mehdi Kargarfard, Fahimeh Esfarjani, Golnaz Vaseghi

Abstract


Background: Recently, the importance of chemokines and their receptors in carcinogenesis and the protective role of aerobic exercise in primary cancer development and progression is highlighted. Based on the facts that endurance exercise may result in hypoxia condition, and in addition, the effect of exercise therapy on the levels of CCL2, CCR2, and their related receptors in breast cancer (BC) model has not been investigated so far, therefore we aimed to evaluate the effect of eight‑week noncontinuous aerobic training on the levels of CCL2, CCL5, and their related receptors; CCR2 and CCR5 in female BALB/C mice with BC. Methods: Thirty‑two BALB/C mice (4–5 weeks old) were randomly divided to four 8‑member groups of control and experimental. The experimental group received 8 weeks of noncontinuous aerobic exercises (AEs) while the control group did not receive any exercises during these 8 weeks. After last of experiment, 5 ml of blood was taken from each rat’s lower inferior vein. The plasma levels of CCL2 and CCL5 were measured by ELISA and CCR2 and CCR5 by western blot. Tumor volume also measured in each step. Data were analyzed using the ANOVA test and the SPSS v. 0.24 Software. Results: After 8 weeks of participation in noncontinuous AEs, a statistically significant decrease was made between the control and experimental groups in terms of CCL2, CCL5, and CCR2 levels, as well as tumor volume. However, there was no significant difference between groups in terms of CCR5 level. Conclusions: It can be concluded that the 8 weeks of noncontinuous AEs did not result in CCR5 reduction while resulting in a statistically significant decrease in CCL2, CCL5, CCR2, and tumor volume.

Keywords


Breast cance; chemokine; CCL2; CCR2; CCL5; CCR5; exercise

Full Text:

PDF

References


Spei ME, Samoli E, Bravi F, La Vecchia C, Bamia C, Benetou V.

Physical activity in breast cancer survivors: A systematic review

and meta‑analysis on overall and breast cancer survival. Breast

;44:144‑52.

Zhong S, Jiang T, Ma T, Zhang X, Tang J, Chen W, et al.

Association between physical activity and mortality in breast

cancer: A meta‑analysis of cohort studies. Eur J Epidemiol

;29:391‑404.

Lee A, Mavaddat N, Wilcox AN, Cunningham AP, Carver T,

Hartley S, et al. BOADICEA: A comprehensive breast cancer

risk prediction model incorporating genetic and nongenetic risk

factors. Genet Med 2019;21:1708‑18.

de Boer MC, Worner EA, Verlaan D, van Leeuwen PA. The

mechanisms and effects of physical activity on breast cancer.

Clin Breast Cancer 2107;17:272‑8.

Delavari MA, Ravasi AA, Gaeini AA, Nouri R. Investigating

the effects eight weeks of noncontinuous aerobic exercise on

the levels of angiopoietin 2‑like protein and interferon beta in

rats suffering from coronary artery disease. Natl J Physiol Pharm

Pharmacol 2018;8:563‑8.

Deep G, Panigrahi GK. Hypoxia‑induced signaling promotes

prostate cancer progression: Exosomes role as messenger of

hypoxic response in tumor microenvironment. Crit Rev Oncog

;20:419‑34.

Murphy EA, Enos RT, Velazquez KT. Influence of exercise on

inflammation in cancer: Direct effect or innocent bystander?

Exerc Sport Sci Rev 2015;43:134‑42.

Hwang JE, Kim HN, Kim DE, Choi HJ, Jung SH, Shim HJ, et al.

Prognostic significance of a systemic inflammatory response in

patients receiving first‑line palliative chemotherapy for recurred

or metastatic gastric cancer. BMC Cancer 2011;11:489.

Gleeson M, Bishop NC, Stensel DJ, Lindley MR, Mastana SS,

Nimmo MA. The anti‑inflammatory effects of exercise:

Mechanisms and implications for the prevention and treatment of

disease. Nat Rev Immunol 2011;11:607‑15.

Strandberg E, Edholm P, Ponsot E, Wahlin‑Larsson B,

Hellmen E, Nilsson A, et al. Influence of combined resistance

training and healthy diet on muscle mass in healthy elderly

women: A randomized controlled trial. J Appl Physiol (1985)

;119:918‑25.

Ali S, Lazennec G. Chemokines: Novel targets for breast cancer

metastasis. Cancer Metastasis Rev 2007;26:401‑20.

Vindrieux D, Escobar P, Lazennec G. Emerging roles of

chemokines in prostate cancer. Endocrine‑Related Cancer

;16:663.‑73.

Svensson S, Abrahamsson A, Rodriguez GV, Olsson AK,

Jensen L, Cao Y, et al. CCL2 and CCL5 are novel therapeutic

targets for estrogen‑dependent breast cancer. Clin Cancer Res

;21:3794‑805.

Nagaiah G, Hazard HW, Abraham J. Role of obesity and exercise

in breast cancer survivors. Oncology 2010;24:342‑6.

Carlin JL, Grissom N, Ying Z, Gomez‑Pinilla F, Reyes TM.

Voluntary exercise blocks Western diet‑induced gene expression

of the chemokines CXCL10 and CCL2 in the prefrontal cortex.

Brain Behav Immun 2016;58:82‑90.

Seruga B, Zhang H, Bernstein LJ, Tannock IF. Cytokines and. their relationship to the symptoms and outcome of cancer. Nat Rev

Cancer 2008;8:887‑99.

Adamopoulos S, Parissis J, Karatzas D, Kroupis C,

Georgiadis M, Karavolias G, et al. Physical training modulates

proinflammatory cytokines and the soluble Fas/soluble Fasligand

system in patients with chronic heart failure. J Am Coll Cardiol

;39:653‑63.

Goldhammer E, Tanchilevitch A, Maor I, Beniamini Y,

Rosenschein U, Sagiv M. Exercise training modulates cytokines

activity in coronary heart disease patients. Int J Cardio

;100:93‑9.

Qian BZ, Li J, Zhang H, Kitamura T, Zhang J, Campion LR,

et al. CCL2 recruits inflammatory monocytes to facilitate

breast‑tumour metastasis. Nature 2011;475:222‑5.

Kang Y. Dissecting tumor‑stromal interactions in breast cancer

bone metastasis. Endocrinol Metab 2016;31:206‑12.

Murphy EA, Davis JM, Barrilleaux TL, McClellan JL,

Steiner JL, Carmichael MD, et al. Benefits of exercise training

on breast cancer progression and inflammation in C3 (1)

SV40Tag mice. Cytokine 2011;55:274‑9.

Raman D, Sobolik‑Delmaire T, Richmond A. Chemokines in

health and disease. Exp Cell Res 2011;317:575‑89.

Gao DF, Fish EN. 89: A role for CCL5 in breast cancer cell

metabolism. Cytokine 2013;63:264.

van Deventer HW, O’Connor W, Brickey WJ, Aris RM, Ting JP,

Serody JS. CC chemokine receptor 5 on stromal cells promotes

pulmonary metastasis. Cancer Res 2005;65:3374‑9.

Tang CH, Yamamoto A, Lin YT, Fong YC, Tan TW.

Involvement of matrix metalloproteinase‑3 in CCL5/CCR5

pathway of chondrosarcomas metastasis. Biochem Pharmacol

;79:209‑17.

Chuang JY, Yang WH, Chen HT, Huang CY, Tan TW, Lin YT,

et al. CCL5/CCR5 axis promotes the motility of human oral

cancer cells. J Cell Physiol 2009;220:418‑26