Exercise in advanced prostate cancer elevates myokine levels and suppresses in-vitro cell growth.
Journal
Prostate cancer and prostatic diseases
ISSN: 1476-5608
Titre abrégé: Prostate Cancer Prostatic Dis
Pays: England
ID NLM: 9815755
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
received:
20
10
2021
accepted:
20
01
2022
pubmed:
14
2
2022
medline:
22
4
2022
entrez:
13
2
2022
Statut:
ppublish
Résumé
Altering the systemic milieu through exercise has been proposed as a potential mechanism underlying exercise-driven tumour suppression. It is not yet known whether men with advanced prostate cancer can elicit such adaptations following a program of exercise. The purpose is to examine myokine levels of serum acquired from metastatic castrate-resistant prostate cancer (mCRPC) patients recruited to the INTERVAL-GAP4 trial before and after 6 months of exercise and its tumour-suppressive effect. Twenty-five men with mCRPC (age = 74.7 ± 7.1 yrs) were randomised to supervised multimodal (aerobic and resistance) exercise (EX) or self-directed exercise control group (CON). Body composition was assessed using dual-energy x-ray absorptiometry (DXA), and fasting blood in a rested state was collected at baseline and at 6 months. Serum levels of myokines (SPARC, OSM, decorin, IGF-1, and IGFBP-3) were measured. Serum was applied to the prostate cancer cell line DU145, and growth was assessed for 72 h. No significant change in body composition was observed. Adjusted serum OSM (P = 0.050) and relative OSM (P = 0.083), serum SPARC (P = 0.022) and relative SPARC (P = 0.025) increased in EX compared to CON. The area under curve (AUC) over 72 h showed a significant reduction in DU145 growth after applying post-intervention serum from the EX vs CON (P = 0.029). Elevated myokine expressions and greater tumour-suppressive effects of serum after 6 months of periodised and autoregulated supervised exercise was observed in men with mCRPC. Exercise-induced systemic changes may slow disease progression in men with advanced prostate cancer.
Sections du résumé
BACKGROUND
Altering the systemic milieu through exercise has been proposed as a potential mechanism underlying exercise-driven tumour suppression. It is not yet known whether men with advanced prostate cancer can elicit such adaptations following a program of exercise. The purpose is to examine myokine levels of serum acquired from metastatic castrate-resistant prostate cancer (mCRPC) patients recruited to the INTERVAL-GAP4 trial before and after 6 months of exercise and its tumour-suppressive effect.
METHODS
Twenty-five men with mCRPC (age = 74.7 ± 7.1 yrs) were randomised to supervised multimodal (aerobic and resistance) exercise (EX) or self-directed exercise control group (CON). Body composition was assessed using dual-energy x-ray absorptiometry (DXA), and fasting blood in a rested state was collected at baseline and at 6 months. Serum levels of myokines (SPARC, OSM, decorin, IGF-1, and IGFBP-3) were measured. Serum was applied to the prostate cancer cell line DU145, and growth was assessed for 72 h.
RESULTS
No significant change in body composition was observed. Adjusted serum OSM (P = 0.050) and relative OSM (P = 0.083), serum SPARC (P = 0.022) and relative SPARC (P = 0.025) increased in EX compared to CON. The area under curve (AUC) over 72 h showed a significant reduction in DU145 growth after applying post-intervention serum from the EX vs CON (P = 0.029).
CONCLUSION
Elevated myokine expressions and greater tumour-suppressive effects of serum after 6 months of periodised and autoregulated supervised exercise was observed in men with mCRPC. Exercise-induced systemic changes may slow disease progression in men with advanced prostate cancer.
Identifiants
pubmed: 35152272
doi: 10.1038/s41391-022-00504-x
pii: 10.1038/s41391-022-00504-x
pmc: PMC8853098
doi:
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
86-92Informations de copyright
© 2022. The Author(s).
Références
Jones LW, Alfano CM. Exercise-oncology research: past, present, and future. Acta Oncol. 2013;52:195–215.
doi: 10.3109/0284186X.2012.742564
pubmed: 23244677
Kenfield SA, Stampfer MJ, Giovannucci E, Chan JM. Physical activity and survival after prostate cancer diagnosis in the health professionals follow-up study. J Clin Oncol. 2011;29:726–32.
doi: 10.1200/JCO.2010.31.5226
pubmed: 21205749
pmcid: 3056656
Richman EL, Kenfield SA, Stampfer MJ, Paciorek A, Carroll PR, Chan JM. Physical activity after diagnosis and risk of prostate cancer progression: data from the cancer of the prostate strategic urologic research endeavor. Cancer Res. 2011;71:3889–95.
doi: 10.1158/0008-5472.CAN-10-3932
pubmed: 21610110
pmcid: 3107352
Hart NH, Galvao DA, Newton RU. Exercise medicine for advanced prostate cancer. Curr Opin Support Palliat Care. 2017;11:247–57.
doi: 10.1097/SPC.0000000000000276
pubmed: 28562375
Kim J-S, Galvão DA, Newton RU, Gray E, Taaffe DR. Exercise-induced myokines and their effect on prostate cancer. Nat Rev Urol. 2021;18:519–42.
doi: 10.1038/s41585-021-00476-y
pubmed: 34158658
Newton RU, Kenfield SA, Hart NH, Chan JM, Courneya KS, Catto J, et al. Intense exercise for survival among men with metastatic castrate-resistant prostate cancer (INTERVAL-GAP4): a multicentre, randomised, controlled phase III study protocol. BMJ Open. 2018;8:e022899.
doi: 10.1136/bmjopen-2018-022899
pubmed: 29764892
pmcid: 5961562
Barnard RJ, Ngo TH, Leung PS, Aronson WJ, Golding LA. A low-fat diet and/or strenuous exercise alters the IGF axis in vivo and reduces prostate tumor cell growth in vitro. Prostate. 2003;56:201–06.
doi: 10.1002/pros.10251
pubmed: 12772189
Dethlefsen C, Hansen LS, Lillelund C, Andersen C, Gehl J, Christensen JF, et al. Exercise-induced catecholamines activate the hippo tumor suppressor pathway to reduce risks of breast cancer development. Cancer Res. 2017;77:4894–904.
doi: 10.1158/0008-5472.CAN-16-3125
pubmed: 28887324
Dethlefsen C, Lillelund C, Midtgaard J, Andersen C, Pedersen BK, Christensen JF, et al. Exercise regulates breast cancer cell viability: systemic training adaptations versus acute exercise responses. Breast Cancer Res Treat. 2016;159:469–79.
doi: 10.1007/s10549-016-3970-1
pubmed: 27601139
Devin JL, Hill MM, Mourtzakis M, Quadrilatero J, Jenkins DG, Skinner TL. Acute high intensity interval exercise reduces colon cancer cell growth. J Physiol. 2019;597:2177–84.
doi: 10.1113/JP277648
pubmed: 30812059
pmcid: 6462486
Leung PS, Aronson WJ, Ngo TH, Golding LA, Barnard RJ. Exercise alters the IGF axis in vivo and increases p53 protein in prostate tumor cells in vitro. J Appl Physiol (1985). 2004;96:450–4.
doi: 10.1152/japplphysiol.00871.2003
Ngo TH, Barnard RJ, Leung PS, Cohen P, Aronson WJ. Insulin-like growth factor I (IGF-I) and IGF binding protein-1 modulate prostate cancer cell growth and apoptosis: possible mediators for the effects of diet and exercise on cancer cell survival. Endocrinology. 2003;144:2319–24.
doi: 10.1210/en.2003-221028
pubmed: 12746292
Rundqvist H, Augsten M, Stromberg A, Rullman E, Mijwel S, Kharaziha P, et al. Effect of acute exercise on prostate cancer cell growth. PLoS One. 2013;8:e67579.
doi: 10.1371/journal.pone.0067579
pubmed: 23861774
pmcid: 3702495
Kim JS, Wilson RL, Taaffe DR, Galvao DA, Gray E, Newton RU. Myokine expression and tumor-suppressive effect of serum following 12 weeks of exercise in prostate cancer patients on ADT. Med Sci Sports Exerc. 2021;54:197–205.
doi: 10.1249/MSS.0000000000002783
pmcid: 8754092
Pedersen BK. The physiology of optimising health with a focus on exercise as medicine. Annu Rev Physiol. 2019;81:607–27.
doi: 10.1146/annurev-physiol-020518-114339
pubmed: 30526319
Gannon NP, Vaughan RA, Garcia-Smith R, Bisoffi M, Trujillo KA. Effects of the exercise-inducible myokine irisin on malignant and non-malignant breast epithelial cell behavior in vitro. Int J Cancer. 2015;136:E197–202.
doi: 10.1002/ijc.29142
pubmed: 25124080
Liu J, Song N, Huang Y, Chen Y. Irisin inhibits pancreatic cancer cell growth via the AMPK-mTOR pathway. Sci Rep. 2018;8:15247.
doi: 10.1038/s41598-018-33229-w
pubmed: 30323244
pmcid: 6189061
Shao L, Li H, Chen J, Song H, Zhang Y, Wu F, et al. Irisin suppresses the migration, proliferation, and invasion of lung cancer cells via inhibition of epithelial-to-mesenchymal transition. Biochem Biophys Res Commun. 2017;485:598–605.
doi: 10.1016/j.bbrc.2016.12.084
pubmed: 27986567
Tekin S, Erden Y, Sandal S, Yilmaz B. Is irisin an anticarcinogenic peptide? Med-Sci. 2015;4:2172–80.
doi: 10.5455/medscience.2014.03.8210
Hu Y, Sun H, Owens RT, Wu J, Chen YQ, Berquin IM, et al. Decorin suppresses prostate tumor growth through inhibition of epidermal growth factor and androgen receptor pathways. Neoplasia. 2009;11:1042–53.
doi: 10.1593/neo.09760
pubmed: 19794963
pmcid: 2745670
Santra M, Eichstetter I, Iozzo RV. An anti-oncogenic role for decorin. Down-regulation of ErbB2 leads to growth suppression and cytodifferentiation of mammary carcinoma cells. J Biol Chem. 2000;275:35153–61.
doi: 10.1074/jbc.M006821200
pubmed: 10942781
Seidler DG, Goldoni S, Agnew C, Cardi C, Thakur ML, Owens RT, et al. Decorin protein core inhibits in vivo cancer growth and metabolism by hindering epidermal growth factor receptor function and triggering apoptosis via caspase-3 activation. J Biol Chem. 2006;281:26408–18.
doi: 10.1074/jbc.M602853200
pubmed: 16835231
Shi X, Liang W, Yang W, Xia R, Song Y. Decorin is responsible for progression of non-small-cell lung cancer by promoting cell proliferation and metastasis. Tumour Biol. 2015;36:3345–54.
doi: 10.1007/s13277-014-2968-8
pubmed: 25524578
Xu W, Neill T, Yang Y, Hu Z, Cleveland E, Wu Y, et al. The systemic delivery of an oncolytic adenovirus expressing decorin inhibits bone metastasis in a mouse model of human prostate cancer. Gene Ther. 2015;22:247–56.
doi: 10.1038/gt.2014.110
pubmed: 25503693
Chung TD, Yu JJ, Spiotto MT, Bartkowski M, Simons JW. Characterisation of the role of IL-6 in the progression of prostate cancer. Prostate. 1999;38:199–207.
doi: 10.1002/(SICI)1097-0045(19990215)38:3<199::AID-PROS4>3.0.CO;2-H
pubmed: 10068344
Lee SO, Chun JY, Nadiminty N, Lou W, Gao AC. Interleukin-6 undergoes transition from growth inhibitor associated with neuroendocrine differentiation to stimulator accompanied by androgen receptor activation during LNCaP prostate cancer cell progression. Prostate. 2007;67:764–73.
doi: 10.1002/pros.20553
pubmed: 17373716
Morris JC, Ramlogan-Steel CA, Yu P, Black BA, Mannan P, Allison JP, et al. Vaccination with tumor cells expressing IL-15 and IL-15Ralpha inhibits murine breast and prostate cancer. Gene Ther. 2014;21:393–401.
doi: 10.1038/gt.2014.10
pubmed: 24572789
pmcid: 3976433
Tang F, Zhao LT, Jiang Y, Ba de N, Cui LX, He W. Activity of recombinant human interleukin-15 against tumor recurrence and metastasis in mice. Cell Mol Immunol. 2008;5:189–96.
doi: 10.1038/cmi.2008.23
pubmed: 18582400
pmcid: 4651289
Aoi W, Naito Y, Takagi T, Tanimura Y, Takanami Y, Kawai Y, et al. A novel myokine, secreted protein acidic and rich in cysteine (SPARC), suppresses colon tumorigenesis via regular exercise. Gut. 2013;62:882–9.
doi: 10.1136/gutjnl-2011-300776
pubmed: 22851666
Said N, Frierson HF Jr, Chernauskas D, Conaway M, Motamed K, Theodorescu D. The role of SPARC in the TRAMP model of prostate carcinogenesis and progression. Oncogene. 2009;28:3487–98.
doi: 10.1038/onc.2009.205
pubmed: 19597474
Said N, Motamed K. Absence of host-secreted protein acidic and rich in cysteine (SPARC) augments peritoneal ovarian carcinomatosis. Am J Pathol. 2005;167:1739–52.
doi: 10.1016/S0002-9440(10)61255-2
pubmed: 16314484
pmcid: 1613196
Yiu GK, Chan WY, Ng SW, Chan PS, Cheung KK, Berkowitz RS, et al. SPARC (secreted protein acidic and rich in cysteine) induces apoptosis in ovarian cancer cells. Am J Pathol. 2001;159:609–22.
doi: 10.1016/S0002-9440(10)61732-4
pubmed: 11485919
pmcid: 1850537
Hojman P, Dethlefsen C, Brandt C, Hansen J, Pedersen L, Pedersen BK. Exercise-induced muscle-derived cytokines inhibit mammary cancer cell growth. Am J Physiol Endocrinol Metab. 2011;301:E504–10.
doi: 10.1152/ajpendo.00520.2010
pubmed: 21653222
Hutt JA, DeWille JW. Oncostatin M induces growth arrest of mammary epithelium via a CCAAT/enhancer-binding protein delta-dependent pathway. Mol Cancer Ther. 2002;1:601–10.
pubmed: 12479220
Liu J, Spence MJ, Wallace PM, Forcier K, Hellstrom I, Vestal RE. Oncostatin M-specific receptor mediates inhibition of breast cancer cell growth and down-regulation of the c-myc proto-oncogene. Cell Growth Differ. 1997;8:667–76.
pubmed: 9186000
Campbell KL, Winters-Stone KM, Wiskemann J, May AM, Schwartz AL, Courneya KS, et al. Exercise guidelines for cancer survivors: Consensus statement from international multidisciplinary roundtable. Med Sci Sports Exerc. 2019;51:2375–90.
doi: 10.1249/MSS.0000000000002116
pubmed: 31626055
pmcid: 8576825
Vickers AJ, Altman DG. Analysing controlled trials with baseline and follow up measurements. BMJ. 2001;323:1123–24.
doi: 10.1136/bmj.323.7321.1123
pubmed: 11701584
pmcid: 1121605
Pak S, Kim MS, Park EY, Kim SH, Lee KH, Joung JY. Association of body composition with survival and treatment efficacy in castration-resistant prostate cancer. Front Oncol. 2020;10:558.
doi: 10.3389/fonc.2020.00558
pubmed: 32363164
pmcid: 7180747
Kos K, Wong S, Tan B, Gummesson A, Jernas M, Franck N, et al. Regulation of the fibrosis and angiogenesis promoter SPARC/osteonectin in human adipose tissue by weight change, leptin, insulin, and glucose. Diabetes. 2009;58:1780–88.
doi: 10.2337/db09-0211
pubmed: 19509023
pmcid: 2712789
Mai S, Grugni G, Mele C, Vietti R, Vigna L, Sartorio A, et al. Irisin levels in genetic and essential obesity: clues for a potential dual role. Sci Rep. 2020;10:1020.
doi: 10.1038/s41598-020-57855-5
pubmed: 31974460
pmcid: 6978420
Galvao DA, Taaffe DR, Spry N, Cormie P, Joseph D, Chambers SK, et al. Exercise preserves physical function in prostate cancer patients with bone metastases. Med Sci Sports Exerc. 2018;50:393–9.
doi: 10.1249/MSS.0000000000001454
pubmed: 29036016
Newton RU, GalvÃO DA, Spry N, Joseph D, Chambers SK, Gardiner RA, et al. Exercise mode specificity for preserving spine and hip bone mineral density in prostate cancer patients. Med Sci Sports Exerc. 2019;51:607–14.
doi: 10.1249/MSS.0000000000001831
pubmed: 30395051