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Erschienen in: Journal of Cancer Research and Clinical Oncology 6/2019

09.04.2019 | Original Article – Cancer Research

Molecular and cellular adaptations to exercise training in skeletal muscle from cancer patients treated with chemotherapy

verfasst von: Andreas Buch Møller, Simon Lønbro, Jean Farup, Thomas Schmidt Voss, Nikolaj Rittig, Jakob Wang, Inger Højris, Ulla Ramer Mikkelsen, Niels Jessen

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 6/2019

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Abstract

Background

A growing body of evidence suggests that exercise training has beneficial effects in cancer patients. The aim of the present study was to investigate the molecular basis underlying these beneficial effects in skeletal muscle from cancer patients.

Methods

We investigated expression of selected proteins involved in cellular processes known to orchestrate adaptation to exercise training by western blot. Skeletal muscle biopsies were sampled from ten cancer patients before and after 4–7 weeks of ongoing chemotherapy, and subsequently after 10 weeks of continued chemotherapy in combination with exercise training. Biopsies from ten healthy matched subjects served as reference.

Results

The expression of the insulin-regulated glucose transporter, GLUT4, increased during chemotherapy and continued to increase during exercise training. A similar trend was observed for ACC, a key enzyme in the biosynthesis and oxidation of fatty acids, but we did not observe any changes in other regulators of substrate metabolism (AMPK and PDH) or mitochondrial proteins (Cyt-C, COX-IV, SDHA, and VDAC). Markers of proteasomal proteolysis (MURF1 and ATROGIN-1) decreased during chemotherapy, but did not change further during chemotherapy combined with exercise training. A similar pattern was observed for autophagy-related proteins such as ATG5, p62, and pULK1 Ser757, but not ULK1 and LC3BII/LC3BI. Phosphorylation of FOXO3a at Ser318/321 did not change during chemotherapy, but decreased during exercise training. This could suggest that FOXO3a-mediated transcriptional regulation of MURF1 and ATROGIN-1 serves as a mechanism by which exercise training maintains proteolytic systems in skeletal muscle in cancer patients. Phosphorylation of proteins that regulate protein synthesis (mTOR at Ser2448 and 4EBP1 at Thr37/46) increased during chemotherapy and leveled off during exercise training. Finally, chemotherapy tended to increase the number of satellite cells in type 1 fibers, without any further change during chemotherapy and exercise training. Conversely, the number of satellite cells in type 2 fibers did not change during chemotherapy, but increased during chemotherapy combined with exercise training.

Conclusions

Molecular signaling cascades involved in exercise training are disturbed during cancer and chemotherapy, and exercise training may prevent further disruption of these pathways.

Trial registration

The study was approved by the local Scientific Ethics Committee of the Central Denmark Region (Project ID: M-2014-15-14; date of approval: 01/27/2014) and the Danish Data Protection Agency (case number 2007-58-0010; date of approval: 01/28/2015). The trial was registered at http/​/​www.​clinicaltrials.​gov (registration number: NCT02192216; date of registration 07/17-2014).
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Literatur
Zurück zum Zitat Coffey VG, Hawley JA (2007) The molecular bases of training adaptation. Sports Med (Auckland, NZ) 37:737–763CrossRef Coffey VG, Hawley JA (2007) The molecular bases of training adaptation. Sports Med (Auckland, NZ) 37:737–763CrossRef
Zurück zum Zitat Collaborators GBDCoD (2017) Global, regional, and national age-sex specific mortality for 264 causes of death, 1980–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet (London, England) 390:1151–1210CrossRef Collaborators GBDCoD (2017) Global, regional, and national age-sex specific mortality for 264 causes of death, 1980–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet (London, England) 390:1151–1210CrossRef
Zurück zum Zitat Lonbro S, Farup J, Bentsen S, Voss TS, Rittig N, Wang J, Ørskov M, Højris I, Mikkelsen UR (2017) Lean body mass, muscle fibre size and muscle function in cancer patients during chemotherapy and 10 weeks of exercise. JCSM Clin Rep 2(1):1–15 Lonbro S, Farup J, Bentsen S, Voss TS, Rittig N, Wang J, Ørskov M, Højris I, Mikkelsen UR (2017) Lean body mass, muscle fibre size and muscle function in cancer patients during chemotherapy and 10 weeks of exercise. JCSM Clin Rep 2(1):1–15
Zurück zum Zitat Moller AB, Vendelbo MH, Rahbek SK, Clasen BF, Schjerling P, Vissing K, Jessen N (2013) Resistance exercise, but not endurance exercise, induces IKKbeta phosphorylation in human skeletal muscle of training-accustomed individuals. Pflugers Arch Eur J Physiol 465:1785–1795. https://doi.org/10.1007/s00424-013-1318-9 CrossRef Moller AB, Vendelbo MH, Rahbek SK, Clasen BF, Schjerling P, Vissing K, Jessen N (2013) Resistance exercise, but not endurance exercise, induces IKKbeta phosphorylation in human skeletal muscle of training-accustomed individuals. Pflugers Arch Eur J Physiol 465:1785–1795. https://​doi.​org/​10.​1007/​s00424-013-1318-9 CrossRef
Zurück zum Zitat Pilegaard H, Saltin B, Neufer PD (2003) Exercise induces transient transcriptional activation of the PGC-1alpha gene in human skeletal muscle. J Physiol 546:851–858CrossRefPubMedPubMedCentral Pilegaard H, Saltin B, Neufer PD (2003) Exercise induces transient transcriptional activation of the PGC-1alpha gene in human skeletal muscle. J Physiol 546:851–858CrossRefPubMedPubMedCentral
Zurück zum Zitat Rahbek SK, Farup J, Moller AB, Vendelbo MH, Holm L, Jessen N, Vissing K (2014) Effects of divergent resistance exercise contraction mode and dietary supplementation type on anabolic signalling, muscle protein synthesis and muscle hypertrophy. Amino Acids 46:2377–2392. https://doi.org/10.1007/s00726-014-1792-1 CrossRef Rahbek SK, Farup J, Moller AB, Vendelbo MH, Holm L, Jessen N, Vissing K (2014) Effects of divergent resistance exercise contraction mode and dietary supplementation type on anabolic signalling, muscle protein synthesis and muscle hypertrophy. Amino Acids 46:2377–2392. https://​doi.​org/​10.​1007/​s00726-014-1792-1 CrossRef
Metadaten
Titel
Molecular and cellular adaptations to exercise training in skeletal muscle from cancer patients treated with chemotherapy
verfasst von
Andreas Buch Møller
Simon Lønbro
Jean Farup
Thomas Schmidt Voss
Nikolaj Rittig
Jakob Wang
Inger Højris
Ulla Ramer Mikkelsen
Niels Jessen
Publikationsdatum
09.04.2019
Verlag
Springer Berlin Heidelberg
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 6/2019
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-019-02911-5

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