Displaced Myonuclei in Cancer Cachexia Suggest Altered Innervation
An idiopathic myopathy characterized by central nuclei in muscle fibers, a hallmark of muscle regeneration, has been observed in cancer patients. In cancer cachexia skeletal muscle is incapable of regeneration, consequently, this observation remains unaccounted for. In C26-tumor bearing, cachectic m...
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doaj-1d90f9f4b4f9449f9043de03cd4996462020-11-25T02:39:21ZengMDPI AGInternational Journal of Molecular Sciences1422-00672020-02-01213109210.3390/ijms21031092ijms21031092Displaced Myonuclei in Cancer Cachexia Suggest Altered InnervationNissrine Daou0Medhi Hassani1Emidio Matos2Gabriela Salim De Castro3Raquel Galvao Figueredo Costa4Marilia Seelaender5Viviana Moresi6Marco Rocchi7Sergio Adamo8Zhenlin Li9Onnik Agbulut10Dario Coletti11Sorbonne Université, Institut de Biologie Paris-Seine (IBPS), CNRS UMR 8256, Inserm ERL U1164, Biological Adaptation and Ageing, F-75005 Paris, FranceSorbonne Université, Institut de Biologie Paris-Seine (IBPS), CNRS UMR 8256, Inserm ERL U1164, Biological Adaptation and Ageing, F-75005 Paris, FranceDepartment of Physical Education, Federal University of Piauí, Teresina 64000-805 PI, BrazilInstitute of Biomedical Sciences, University of Sao Paulo, Sao Paulo 05508-000 SP, BrazilInstitute of Biomedical Sciences, University of Sao Paulo, Sao Paulo 05508-000 SP, BrazilInstitute of Biomedical Sciences, University of Sao Paulo, Sao Paulo 05508-000 SP, BrazilDAHFMO Unit of Histology and Medical Embryology, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, ItalyDAHFMO Unit of Histology and Medical Embryology, Sapienza University of Rome, 00161 Rome, ItalySorbonne Université, Institut de Biologie Paris-Seine (IBPS), CNRS UMR 8256, Inserm ERL U1164, Biological Adaptation and Ageing, F-75005 Paris, FranceSorbonne Université, Institut de Biologie Paris-Seine (IBPS), CNRS UMR 8256, Inserm ERL U1164, Biological Adaptation and Ageing, F-75005 Paris, FranceSorbonne Université, Institut de Biologie Paris-Seine (IBPS), CNRS UMR 8256, Inserm ERL U1164, Biological Adaptation and Ageing, F-75005 Paris, FranceAn idiopathic myopathy characterized by central nuclei in muscle fibers, a hallmark of muscle regeneration, has been observed in cancer patients. In cancer cachexia skeletal muscle is incapable of regeneration, consequently, this observation remains unaccounted for. In C26-tumor bearing, cachectic mice, we observed muscle fibers with central nuclei in the absence of molecular markers of bona fide regeneration. These clustered, non-peripheral nuclei were present in NCAM-expressing muscle fibers. Since NCAM expression is upregulated in denervated myofibers, we searched for additional makers of denervation, including AchRs, MUSK, and HDAC. This last one being also consistently upregulated in cachectic muscles, correlated with an increase of central myonuclei. This held true in the musculature of patients suffering from gastrointestinal cancer, where a progressive increase in the number of central myonuclei was observed in weight stable and in cachectic patients, compared to healthy subjects. Based on all of the above, the presence of central myonuclei in cancer patients and animal models of cachexia is consistent with motor neuron loss or NMJ perturbation and could underlie a previously neglected phenomenon of denervation, rather than representing myofiber damage and regeneration in cachexia. Similarly to aging, denervation-dependent myofiber atrophy could contribute to muscle wasting in cancer cachexia.https://www.mdpi.com/1422-0067/21/3/1092central nucleimuscle regenerationstriated musclesc26-colon carcinomacancer cachexiaaltered innervation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nissrine Daou Medhi Hassani Emidio Matos Gabriela Salim De Castro Raquel Galvao Figueredo Costa Marilia Seelaender Viviana Moresi Marco Rocchi Sergio Adamo Zhenlin Li Onnik Agbulut Dario Coletti |
spellingShingle |
Nissrine Daou Medhi Hassani Emidio Matos Gabriela Salim De Castro Raquel Galvao Figueredo Costa Marilia Seelaender Viviana Moresi Marco Rocchi Sergio Adamo Zhenlin Li Onnik Agbulut Dario Coletti Displaced Myonuclei in Cancer Cachexia Suggest Altered Innervation International Journal of Molecular Sciences central nuclei muscle regeneration striated muscles c26-colon carcinoma cancer cachexia altered innervation |
author_facet |
Nissrine Daou Medhi Hassani Emidio Matos Gabriela Salim De Castro Raquel Galvao Figueredo Costa Marilia Seelaender Viviana Moresi Marco Rocchi Sergio Adamo Zhenlin Li Onnik Agbulut Dario Coletti |
author_sort |
Nissrine Daou |
title |
Displaced Myonuclei in Cancer Cachexia Suggest Altered Innervation |
title_short |
Displaced Myonuclei in Cancer Cachexia Suggest Altered Innervation |
title_full |
Displaced Myonuclei in Cancer Cachexia Suggest Altered Innervation |
title_fullStr |
Displaced Myonuclei in Cancer Cachexia Suggest Altered Innervation |
title_full_unstemmed |
Displaced Myonuclei in Cancer Cachexia Suggest Altered Innervation |
title_sort |
displaced myonuclei in cancer cachexia suggest altered innervation |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2020-02-01 |
description |
An idiopathic myopathy characterized by central nuclei in muscle fibers, a hallmark of muscle regeneration, has been observed in cancer patients. In cancer cachexia skeletal muscle is incapable of regeneration, consequently, this observation remains unaccounted for. In C26-tumor bearing, cachectic mice, we observed muscle fibers with central nuclei in the absence of molecular markers of bona fide regeneration. These clustered, non-peripheral nuclei were present in NCAM-expressing muscle fibers. Since NCAM expression is upregulated in denervated myofibers, we searched for additional makers of denervation, including AchRs, MUSK, and HDAC. This last one being also consistently upregulated in cachectic muscles, correlated with an increase of central myonuclei. This held true in the musculature of patients suffering from gastrointestinal cancer, where a progressive increase in the number of central myonuclei was observed in weight stable and in cachectic patients, compared to healthy subjects. Based on all of the above, the presence of central myonuclei in cancer patients and animal models of cachexia is consistent with motor neuron loss or NMJ perturbation and could underlie a previously neglected phenomenon of denervation, rather than representing myofiber damage and regeneration in cachexia. Similarly to aging, denervation-dependent myofiber atrophy could contribute to muscle wasting in cancer cachexia. |
topic |
central nuclei muscle regeneration striated muscles c26-colon carcinoma cancer cachexia altered innervation |
url |
https://www.mdpi.com/1422-0067/21/3/1092 |
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