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

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 reflec...

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Bibliographic Details
Published in:Cancers 2020-11, Vol.12 (11), p.3221
Main Authors: Massart, Isabelle S., Paulissen, Geneviève, Loumaye, Audrey, Lause, Pascale, Pötgens, Sarah A., Thibaut, Morgane M., Balan, Estelle, Deldicque, Louise, Atfi, Azeddine, Louis, Edouard, Gruson, Damien, Bindels, Laure B., Meuwis, Marie-Alice, Thissen, Jean-Paul
Format: Article
Language:English
Subjects:
acute phase reactants
Cachexia
Cancer
Causes of
Complications and side effects
Development and progression
Gastroenterology & hepatology
Gastroentérologie & hépatologie
Human health sciences
Muscles
Physiological aspects
proteomics
Sciences de la santé humaine
secretome
skeletal muscle
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Summary: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.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers12113221