Muscle and cancer: a bidirectional relationship. Pathophysiology and consequences

Authors

  • Lluvia Itzel León-Reyes Servicio de Neuropediatría, Centro Médico Nacional 20 de Noviembre, Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado (ISSSTE). Programa de Maestría en Ciencias de la Salud, Escuela Superior de Medicina, Instituto Politécnico Nacional. Ciudad de México, México.
  • Patricia Canto Unidad de Investigación en Obesidad, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM). Subdirección de Investigación Clínica, Dirección de Investigación, Instituto Nacional de Ciencias Médicas y Nutrición «Salvador Zubirán». Ciudad de México, México.
  • Ramón M Coral-Vázquez Sección de Estudios de Postgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional. Subdirección de Enseñanza e Investigación, Centro Médico Nacional 20 de Noviembre, Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado (ISSSTE). Ciudad de México, México.

DOI:

https://doi.org/10.35366/112699

Keywords:

sarcopenia, cancer, mortality, survival, chemotherapy, radiotherapy

Abstract

The muscle has very important interrelationships with other organs such as the heart, liver, brain and adipose tissue. Its wear, known as sarcopenia, has been associated with different types of cancer during treatment, which causes an increase in toxicity derived from both, chemotherapy and radiotherapy. This causes treatment delays and unwanted dose adjustments that negatively impact the survival of cancer patients. There is evidence that suggests that sarcopenia persists even in the survival stage, conditioning a negative impact on the quality of life of patients and on their work productivity. Different physiopathological mechanisms at the cellular and molecular level involved in sarcopenia in cancer are known, which increasingly show a bidirectional relationship, both positive and negative, between cancer and muscle. 

References

Lee JH, Jun HS. Role of myokines in regulating skeletal

muscle mass and function. Front Physiol. 2019; 10: 42.

Available in: https://doi.org/10.3389/fphys.2019.00042

Chen W, Wang L, You W, Shan T. Myokines mediate

the cross talk between skeletal muscle and other organs.

J Cell Physiol. 2021; 236 (4): 2393-2412. Available in:

https://doi.org/10.1002/jcp.30033

Peixoto da Silva S, Santos JMO, Costa ESMP, Gil

da Costa RM, Medeiros R. Cancer cachexia and its

pathophysiology: links with sarcopenia, anorexia and

asthenia. J Cachexia Sarcopenia Muscle. 2020; 11

(3): 619-635. Available in: https://doi.org/10.1002/

jcsm.12528

Ryan AM, Power DG, Daly L, Cushen SJ, Ni Bhuachalla

E, Prado CM. Cancer-associated malnutrition, cachexia

and sarcopenia: the skeleton in the hospital closet 40

years later. Proc Nutr Soc. 2016; 75 (2): 199-211. Available

in: https://doi.org/10.1017/S002966511500419X

Ness KK, Hudson MM, Pui CH, Green DM, Krull

KR, Huang TT et al. Neuromuscular impairments

in adult survivors of childhood acute lymphoblastic

leukemia: associations with physical performance and

chemotherapy doses. Cancer. 2012; 118 (3): 828-838.

Available in: https://doi.org/10.1002/cncr.26337

Khal J, Wyke SM, Russell ST, Hine AV, Tisdale MJ.

Expression of the ubiquitin-proteasome pathway and

muscle loss in experimental cancer cachexia. Br J

Cancer. 2005; 93 (7): 774-780. Available in: https://doi.

org/10.1038/sj.bjc.6602780

White JP, Baynes JW, Welle SL, Kostek MC, Matesic LE,

Sato S et al. The regulation of skeletal muscle protein

turnover during the progression of cancer cachexia in

the Apc(Min/+) mouse. PLoS One. 2011; 6 (9): e24650.

https://doi.org/10.1371/journal.pone.0024650

Hartman A, Van den Bos C, Stijnen T, Pieters R.

Decrease in peripheral muscle strength and ankle

dorsiflexion as long-term side effects of treatment

for childhood cancer. Pediatr Blood Cancer. 2008;

(4): 833-837. Available in: https://doi.org/10.1002/

pbc.21325

Global Burden of Disease Cancer C, Kocarnik JM,

Compton K, Dean FE, Fu W, Gaw BL et al. Cancer

Incidence, Mortality, Years of Life Lost, Years Lived

With Disability, and Disability-Adjusted Life Years for

Cancer Groups From 2010 to 2019: A Systematic

Analysis for the Global Burden of Disease Study 2019.

JAMA Oncol. 2022; 8 (3): 420-444.

Bauer J, Morley JE, Schols A, Ferrucci L, Cruz-Jentoft

AJ, Dent E et al. Sarcopenia: a time for action. An SCWD

position paper. J Cachexia Sarcopenia Muscle. 2019;

(5): 956-961. Available in: https://doi.org/10.1002/

jcsm.12483

Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyere

O, Cederholm T, Cooper C et al. Sarcopenia: revised

European consensus on definition and diagnosis. Age

Ageing. 2019; 48 (4): 601. Available in: https://doi.

org/10.1093/ageing/afz046

Xu J, Wan CS, Ktoris K, Reijnierse EM, Maier AB.

Sarcopenia Is Associated with Mortality in Adults: A

Systematic Review and Meta-Analysis. Gerontology.

; 68 (4): 361-376. Available in: https://doi.

org/10.1159/000517099

Ritz A, Lurz E, Berger M. Sarcopenia in children with

solid organ tumors: an instrumental era. Cells. 2022;

(8): 1278. Available in: https://doi.org/10.3390/

cells11081278

Ormsbee MJ, Prado CM, Ilich JZ, Purcell S, Siervo M,

Folsom A, Panton L. Osteosarcopenic obesity: the role of

bone, muscle, and fat on health. J Cachexia Sarcopenia

Muscle. 2014; 5 (3): 183-192. Available in: https://doi.

org/10.1007/s13539-014-0146-x

Waters DL, Baumgartner RN. Sarcopenia and obesity.

Clin Geriatr Med. 2011; 27 (3): 401-421. Available in:

https://doi.org/10.1016/j.cger.2011.03.007

Villasenor A, Ballard-Barbash R, Baumgartner K,

Baumgartner R, Bernstein L, McTiernan A et al.

Prevalence and prognostic effect of sarcopenia in

breast cancer survivors: the HEAL Study. J Cancer

Surviv. 2012; 6 (4): 398-406. Available in: https://doi.

org/10.1007/s11764-012-0234-x

Williams AM, Krull KR, Howell CR, Banerjee P,

Brinkman TM, Kaste SC et al. Physiologic frailty and

neurocognitive decline among young-adult childhood

cancer survivors: a prospective study from the St

Jude Lifetime cohort. J Clin Oncol, 2021; 39 (31):

-3495. Available in: https://doi.org/10.1200/

JCO.21.00194

Tomlinson D, Zupanec S, Jones H, O’Sullivan C, Hesser

T, Sung L. The lived experience of fatigue in children and

adolescents with cancer: a systematic review. Support

Care Cancer. 2016; 24 (8): 3623-3631. Available in:

https://doi.org/10.1007/s00520-016-3253-8

Prado CM, Baracos VE, McCargar LJ, Reiman

T, Mourtzakis M, Tonkin K et al. Sarcopenia as a

determinant of chemotherapy toxicity and time to

tumor progression in metastatic breast cancer patients

receiving capecitabine treatment. Clin Cancer Res.

; 15 (8): 2920-2926. Available in: https://doi.

org/10.1158/1078-0432.CCR-08-2242

Cao A, Ferrucci LM, Caan BJ, Irwin ML. Effect of

exercise on sarcopenia among cancer survivors: a

systematic review. Cancers (Basel). 2022; 14 (3).

Available in: https://doi.org/10.3390/cancers14030786

Prado CM, Cushen SJ, Orsso CE, Ryan AM. Sarcopenia

and cachexia in the era of obesity: clinical and nutritional

impact. Proc Nutr Soc. 2016; 75 (2): 188-198. Available

in: https://doi.org/10.1017/S0029665115004279

Brown JL, Lee DE, Rosa-Caldwell ME, Brown LA,

Perry RA, Haynie WS et al. Protein imbalance in the

development of skeletal muscle wasting in tumour-bearing

mice. J Cachexia Sarcopenia Muscle. 2018; 9 (5): 987-

Available in: https://doi.org/10.1002/jcsm.12354

Bechet D, Tassa A, Taillandier D, Combaret L, Attaix D.

Lysosomal proteolysis in skeletal muscle. Int J Biochem

Cell Biol. 2005; 37 (10): 2098-2114. Available in: https://

doi.org/10.1016/j.biocel.2005.02.029

Glick D, Barth S, Macleod KF. Autophagy: cellular and

molecular mechanisms. J Pathol. 2010; 221 (1): 3-12.

Available in: https://doi.org/10.1002/path.2697

Pettersen K, Andersen S, Degen S, Tadini V, Grosjean

J, Hatakeyama S et al. Cancer cachexia associates

with a systemic autophagy-inducing activity mimicked

by cancer cell-derived IL-6 trans-signaling. Sci Rep.

; 7 (1): 2046. Available in: https://doi.org/10.1038/

s41598-017-02088-2

Kraft CS, LeMoine CM, Lyons CN, Michaud D, Mueller

CR, Moyes CD. Control of mitochondrial biogenesis

during myogenesis. Am J Physiol Cell Physiol. 2006; 290

(4): C1119-1127. Available in: https://doi.org/10.1152/

ajpcell.00463.2005

Mallard J, Hucteau E, Charles AL, Bender L, Baeza

C, Pelissie M et al. Chemotherapy impairs skeletal

muscle mitochondrial homeostasis in early breast

cancer patients. J Cachexia Sarcopenia Muscle. 2022;

(3): 1896-1907. Available in: https://doi.org/10.1002/

jcsm.12991

Berg HE, Eiken O, Miklavcic L, Mekjavic IB. Hip, thigh

and calf muscle atrophy and bone loss after 5-week

bedrest inactivity. Eur J Appl Physiol. 2007; 99 (3):

-289. Available in: https://doi.org/10.1007/s00421-

-0346-y

Evans WJ. Skeletal muscle loss: cachexia, sarcopenia,

and inactivity. Am J Clin Nutr. 2010; 91 (4): 1123S-1127S.

Available in: https://doi.org/10.3945/ajcn.2010.28608A

Costelli P, Muscaritoli M, Bossola M, Penna F, Reffo P,

Bonetto A et al. IGF-1 is downregulated in experimental

cancer cachexia. Am J Physiol Regul Integr Comp

Physiol. 2006; 291 (3): R674-683. Available in: https://

doi.org/10.1152/ajpregu.00104.2006

Dirks-Naylor AJ, Griffiths CL. Glucocorticoid-induced

apoptosis and cellular mechanisms of myopathy. J

Steroid Biochem Mol Biol. 2009; 117 (1-3): 1-7. Available

in: https://doi.org/10.1016/j.jsbmb.2009.05.014

Sambasivan R, Tajbakhsh S. Adult skeletal muscle

stem cells. Results Probl Cell Differ. 2015; 56: 191-213.

Available in: https://doi.org/10.1007/978-3-662-44608-

_9

Michele DE. Mechanisms of skeletal muscle repair and

regeneration in health and disease. FEBS J. 2022; 289

(21): 6460-6462. Available in: https://doi.org/10.1111/

febs.16577

Bentzinger CF, Wang YX, Dumont NA, Rudnicki MA.

Cellular dynamics in the muscle satellite cell niche.

EMBO Rep. 2013; 14 (12): 1062-1072. Available in:

https://doi.org/10.1038/embor.2013.182

Tedesco FS, Dellavalle A, Diaz-Manera J, Messina

G, Cossu G. Repairing skeletal muscle: regenerative

potential of skeletal muscle stem cells. J Clin Invest.

; 120 (1): 11-19. https://doi.org/10.1172/JCI40373

Kim J, Lee J. Role of transforming growth factor-beta

in muscle damage and regeneration: focused on

eccentric muscle contraction. J Exerc Rehabil. 2017;

(6): 621-626. Available in: https://doi.org/10.12965/

jer.1735072.536

Ballinger TJ, Thompson WR, Guise TA. The bone-

muscle connection in breast cancer: implications and

therapeutic strategies to preserve musculoskeletal

health. Breast Cancer Res. 2022; 24 (1): 84. Available

in: https://doi.org/10.1186/s13058-022-01576-2

Davis MP, Panikkar R. Sarcopenia associated with

chemotherapy and targeted agents for cancer therapy.

Ann Palliat Med. 2019; 8 (1): 86-101. Available in: https://

doi.org/10.21037/apm.2018.08.02

Marques VA, Ferreira-Junior JB, Lemos TV, Moraes RF,

Junior JRS, Alves RR et al. Effects of chemotherapy

treatment on muscle strength, quality of life, fatigue, and

anxiety in women with breast cancer. Int J Environ Res

Public Health. 2020; 17 (19): 7289. Available in: https://

doi.org/10.3390/ijerph17197289

Braun TP, Szumowski M, Levasseur PR, Grossberg

AJ, Zhu X, Agarwal A et al. Muscle atrophy in response

to cytotoxic chemotherapy is dependent on intact

glucocorticoid signaling in skeletal muscle. PLoS

One. 2014; 9 (9): e106489. Available in: https://doi.

org/10.1371/journal.pone.0106489

Damrauer JS, Stadler ME, Acharyya S, Baldwin AS,

Couch ME, Guttridge DC. Chemotherapy-induced

muscle wasting: association with NF-kappaB and

cancer cachexia. Eur J Transl Myol. 2018; 28 (2): 7590.

Available in: https://doi.org/10.4081/ejtm.2018.7590

Barreto R, Waning DL, Gao H, Liu Y, Zimmers

TA, Bonetto A. Chemotherapy-related cachexia is

associated with mitochondrial depletion and the

activation of ERK1/2 and p38 MAPKs. Oncotarget,

; 7 (28): 43442-43460. Available in: https://doi.

org/10.18632/oncotarget.9779

Chen JL, Colgan TD, Walton KL, Gregorevic P, Harrison

CA. The TGF-beta Signalling Network in Muscle

Development, Adaptation and Disease. Adv Exp Med

Biol. 2016; 900: 97-131. https://doi.org/10.1007/978-3-

-27511-6_5

Yu Y, Feng XH. TGF-beta signaling in cell fate control

and cancer. Curr Opin Cell Biol. 2019; 61: 56-63.

Available in: https://doi.org/10.1016/j.ceb.2019.07.007

Huang L, Li W, Lu Y, Ju Q, Ouyang M. Iron metabolism

in colorectal cancer. Front Oncol. 2023; 13: 1098501.

Available in: https://doi.org/10.3389/fonc.2023.1098501

Okazaki Y, Hino K. Iron and cancer: a special issue.

Cancers (Basel). 2023; 15 (7): Available in: https://doi.

org/10.3390/cancers15072097

Wyart E, Hsu MY, Sartori R, Mina E, Rausch V, Pierobon

ES et al. Iron supplementation is sufficient to rescue

skeletal muscle mass and function in cancer cachexia.

EMBO Rep. 2022; 23 (4): e53746. Available in: https://

doi.org/10.15252/embr.202153746

Arpke RW, Shams AS, Collins BC, Larson AA, Lu N,

Lowe DA et al. Preservation of satellite cell number

and regenerative potential with age reveals locomotory

muscle bias. Skelet Muscle. 2021; 11 (1): 22. Available

in: https://doi.org/10.1186/s13395-021-00277-2

Fukada SI, Higashimoto T, Kaneshige A. Differences

in muscle satellite cell dynamics during muscle

hypertrophy and regeneration. Skelet Muscle. 2022; 12

(1): 17. Available in: https://doi.org/10.1186/s13395-022-

-0

Dumont NA, Bentzinger CF, Sincennes MC, Rudnicki

MA. Satellite cells and skeletal muscle regeneration.

Compr Physiol. 2015; 5 (3): 1027-1059. Available in:

https://doi.org/10.1002/cphy.c140068

Zeng X, Xie L, Ge Y, Zhou Y, Wang H, Chen Y, et al.

Satellite cells are activated in a rat model of radiation-

induced muscle fibrosis. Radiat Res. 2022; 197 (6):

-649. Available in: https://doi.org/10.1667/RADE-

-00183.1

Caiozzo VJ, Giedzinski E, Baker M, Suarez T, Izadi A,

Lan M, et al. The radiosensitivity of satellite cells: cell

cycle regulation, apoptosis and oxidative stress. Radiat

Res. 2010; 174 (5): 582-589. Available in: https://doi.

org/10.1667/RR2190.1

Paulino AC, Wen BC, Brown CK, Tannous R, Mayr

NA, Zhen WK et al. Late effects in children treated with

radiation therapy for Wilms’ tumor. Int J Radiat Oncol

Biol Phys. 2000; 46 (5): 1239-1246. Available in: https://

doi.org/10.1016/s0360-3016(99)00534-9

D’Souza D, Roubos S, Larkin J, Lloyd J, Emmons

R, Chen H et al. The late effects of radiation therapy

on skeletal muscle morphology and progenitor cell

content are influenced by diet-induced obesity and

exercise training in male mice. Sci Rep. 2019; 9 (1):

Available in: https://doi.org/10.1038/s41598-019-

-8

Jung HW, Kim JW, Kim JY, Kim SW, Yang HK, Lee

JW et al. Effect of muscle mass on toxicity and survival

in patients with colon cancer undergoing adjuvant

chemotherapy. Support Care Cancer. 2015; 23 (3):

-694. Available in: https://doi.org/10.1007/s00520-

-2418-6

Schakman O, Gilson H, Thissen JP. Mechanisms of

glucocorticoid-induced myopathy. J Endocrinol. 2008;

(1): 1-10. Available in: https://doi.org/10.1677/JOE-

-0606

Chapman MA, Meza R, Lieber RL. Skeletal muscle

fibroblasts in health and disease. Differentiation. 2016;

(3): 108-115. Available in: https://doi.org/10.1016/j.

diff.2016.05.007

Case AA, Kullgren J, Anwar S, Pedraza S, Davis

MP. Treating chronic pain with buprenorphine-the

practical guide. Curr Treat Options Oncol. 2021; 22

(12): 116. Available in: https://doi-org.pbidi.unam.

mx:2443/10.1007/s11864-021-00910-8

Lin T, Dai M, Xu P, Sun L, Shu X, Xia X et al. Prevalence

of sarcopenia in pain patients and correlation between

the two conditions: a systematic review and meta-

analysis. J Am Med Dir Assoc. 2022; 23 (5): 902.

e1-902.e20. Available in: https://doi-org.pbidi.unam.

mx:2443/10.1016/j.jamda.2022.02.005

Mucke M, Weier M, Carter C, Copeland J, Degenhardt

L, Cuhls H et al. Systematic review and meta-analysis

of cannabinoids in palliative medicine. J Cachexia

Sarcopenia Muscle. 2018; 9 (2): 220-234. Available in:

https://doi-org.pbidi.unam.mx:2443/10.1002/jcsm.12273

Schouten M, Dalle S, Koppo K. Molecular Mechanisms

Through Which Cannabidiol May Affect Skeletal Muscle

Metabolism, Inflammation, Tissue Regeneration, and

Anabolism: A Narrative Review. Cannabis Cannabinoid

Res. 2022; 7(6): 745-757.

Overholser LS, Callaway C. Preventive health in cancer

survivors: what should we be recommending? J Natl

Compr Canc Netw. 2018; 16 (10): 1251-1258. Available

in: https://doi.org/10.6004/jnccn.2018.7083

Pérez CDA, Allende PSR, Verastegui AE, Rivera

FMM, Meneses GA, Herrera GA et al. Assessment

and impact of phase angle and sarcopenia in palliative

cancer patients. Nutr Cancer. 2017; 69 (8): 1227-1233.

Available in: https://doi-org.pbidi.unam.mx:2443/10.108

/01635581.2017.1367939

Ruiz-Casado A, Alvarez-Bustos A, de Pedro CG,

Mendez-Otero M, Romero-Elias M. Cancer-related

fatigue in breast cancer survivors: a review. Clin Breast

Cancer. 2021; 21 (1): 10-25. Available in: https://doi.

org/10.1016/j.clbc.2020.07.011

Van Deuren S, Boonstra A, Van Dulmen-den Broeder

E, Blijlevens N, Knoop H, Loonen J. Severe fatigue after

treatment for childhood cancer. Cochrane Database

Syst Rev. 2020; 3: CD012681. Available in: https://doi.

org/10.1002/14651858.CD012681.pub2

Lee SJ, Park YJ, Cartmell KB. Sarcopenia in cancer

survivors is associated with increased cardiovascular

disease risk. Support Care Cancer. 2018; 26 (7): 2313-

Available in: https://doi.org/10.1007/s00520-018-

-7

Goodenough CG, Partin RE, Ness KK. Skeletal muscle

and childhood cancer: where are we now and where

we go from here. Aging Cancer. 2021; 2 (1-2): 13-35.

Available in: https://doi.org/10.1002/aac2.12027

Hockenberry-Eaton M, Hinds PS. Fatigue in children

and adolescents with cancer: evolution of a program

of study. Semin Oncol Nurs. 2000; 16 (4): 261-

; discussion 272-268. Available in: https://doi.

org/10.1053/sonu.2000.16577

Van Dijk-Lokkart EM, Steur LMH, Braam KI, Veening

MA, Huisman J, Takken T et al. Longitudinal

development of cancer-related fatigue and physical

activity in childhood cancer patients. Pediatr Blood

Cancer. 2019; 66 (12): e27949. Available in: https://

doi.org/10.1002/pbc.27949

Paulino AC. Late effects of radiotherapy for pediatric

extremity sarcomas. Int J Radiat Oncol Biol Phys. 2004;

(1): 265-274. Available in: https://doi.org/10.1016/j.

ijrobp.2004.02.001

Stokes CL, Stokes WA, Kalapurakal JA, Paulino AC,

Cost NG, Cost CR et al. Timing of radiation therapy

in pediatric Wilms tumor: a report from the national

cancer database. Int J Radiat Oncol Biol Phys. 2018;

(2): 453-461. Available in: https://doi.org/10.1016/j.

ijrobp.2018.01.110

Hetzler KL, Hardee JP, Puppa MJ, Narsale AA, Sato

S, Davis JM et al. Sex differences in the relationship of

IL-6 signaling to cancer cachexia progression. Biochim

Biophys Acta. 2015; 1852 (5): 816-825. Available in:

https://doi.org/10.1016/j.bbadis.2014.12.015

Hetzler KL, Hardee JP, LaVoie HA, Murphy EA, Carson

JA. Ovarian function’s role during cancer cachexia

progression in the female mouse. Am J Physiol

Endocrinol Metab. 2017; 312 (5): E447-E459. Available

in: https://doi.org/10.1152/ajpendo.00294.2016

Wang X, Pickrell AM, Zimmers TA, Moraes CT. Increase

in muscle mitochondrial biogenesis does not prevent

muscle loss but increased tumor size in a mouse model

of acute cancer-induced cachexia. PLoS One. 2012; 7

(3): e33426. Available in: https://doi.org/10.1371/journal.

pone.0033426

Downloads

Published

2024-06-06

How to Cite

1.
León-Reyes LI, Canto P, Coral-Vázquez RM. Muscle and cancer: a bidirectional relationship. Pathophysiology and consequences. Invest. Discapacidad [Internet]. 2024 Jun. 6 [cited 2024 Dec. 22];9(3):136-4. Available from: https://dsm.inr.gob.mx/indiscap/index.php/INDISCAP/article/view/51

Issue

Vol. 9 No. 3 (2023)

Section

Evidence synthesis and meta-research

License

Copyright (c) 2023 Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

© Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra under a Creative Commons Attribution 4.0 International (CC BY 4.0) license which allows to reproduce and modify the content if appropiate recognition to the original source is given.

Most read articles by the same author(s)

Similar Articles

1 2 > >> 

You may also start an advanced similarity search for this article.