Marked Increased Production of Acute Phase Reactants by Skeletal Muscle during Cancer Cachexia

Autor: Louise Deldicque, Morgane M. Thibaut, Damien Gruson, Pascale Lause, Edouard Louis, Audrey Loumaye, Sarah A. Pötgens, Geneviève Paulissen, Azeddine Atfi, Laure B. Bindels, Marie-Alice Meuwis, Isabelle S Massart, Jean-Paul Thissen, Estelle Balan
Přispěvatelé: UCL - SSS/IONS - Institute of NeuroScience, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - SSS/IREC/EDIN - Pôle d'endocrinologie, diabète et nutrition, UCL - SSS/LDRI - Louvain Drug Research Institute, UCL - (SLuc) Service d'endocrinologie et de nutrition, UCL - (SLuc) Service de biochimie médicale
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Cancers
Volume 12
Issue 11
Cancers, Vol. 12, no.11, p. 3221 [1-24] (2020)
Cancers, Vol 12, Iss 3221, p 3221 (2020)
ISSN: 2072-6694
Popis: Simple Summary Muscle wasting during cancer is recognized as an independent predictor of mortality. The aim of this study was to characterize the changes in the muscle secretome associated with cancer cachexia to gain a better understanding of the mechanisms involved and to identify secreted proteins which may reflect this wasting process. Our study demonstrated that skeletal muscle is a source of several acute phase reactants during cancer cachexia that may hold the key to a cachexia-specific signature. Future work will have to determine whether some of these acute phase reactants contribute to and/or reflect the muscle atrophy caused by cancer, therefore representing potential therapeutic targets and/or biomarkers of cancer cachexia. Abstract Loss of skeletal muscle mass in cancer cachexia is recognized as a predictor of mortality. This study aimed to characterize the changes in the muscle secretome associated with cancer cachexia to gain a better understanding of the mechanisms involved and to identify secreted proteins which may reflect this wasting process. The changes in the muscle proteome of the C26 model were investigated by label-free proteomic analysis followed by a bioinformatic analysis in order to identify potentially secreted proteins. Multiple reaction monitoring and Western blotting were used to verify the presence of candidate proteins in the circulation. Our results revealed a marked increased muscular production of several acute phase reactants (APR: Haptoglobin, Serine protease inhibitor A3N, Complement C3, Serum amyloid A-1 protein) which are released in the circulation during C26 cancer cachexia. This was confirmed in other models of cancer cachexia as well as in cancer patients. Glucocorticoids and proinflammatory cytokines are responsible for an increased production of APR by muscle cells. Finally, their muscular expressions are strongly positively correlated with body weight loss as well as the muscular induction of atrogens. Our study demonstrates therefore a marked increased production of APR by the muscle in cancer cachexia.
Databáze: OpenAIRE
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