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PXD019433

PXD019433 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMarked increased production of acute phase reactants by skeletal muscle during cancer cachexia
DescriptionBackground Loss of skeletal muscle mass in cancer cachexia is recognized as an independent predictor of mortality. Mechanisms involved in this wasting process and parameters for early diagnosis are not yet clearly defined. As skeletal muscle is considered as a secretory organ, the aim of this present experimental work was to characterize the changes in the putative muscle secretome associated with cancer-induced cachexia to gain a better understanding of cellular mechanisms involved and to identify secreted proteins which might reflect this wasting process. Methods We investigated first the changes in the muscle proteome associated with cancer-induced cachexia by using differential label-free proteomic analysis on muscle of the C26 mouse model. The differentially abundant proteins were then submitted to sequential bioinformatic secretomic analysis in order to identify potentially secreted proteins. Multiple reaction monitoring and Western blotting were used to verify the presence of candidate proteins at the circulating level. Finally, we investigated the regulation of the production of these secreted proteins by muscle in vitro and in vivo. Results Our results revealed a dramatic increased muscular production (2-to 25-fold) of several acute phase reactants (APR: haptoglobin, serpina3n, complement C3, serum amyloid A1) which are released in the circulation during C26 cancer cachexia. This observation was confirmed in two other preclinical models of cancer cachexia as well as in cancer patients. The muscular origin of these APR was demonstrated by their increased expression in skeletal muscle and myotubes. Our results showed also that IL-6 plays a major role in the muscular induction of these APR in vivo, while glucocorticoids and pro-inflammatory cytokines stimulate directly their increased expression in muscle cells in vitro. Conclusions Muscle wasting caused by cancer is associated with marked changes in muscle secretome. Our study demonstrates a marked increased production of APR by skeletal muscle in pre-clinical models of cancer cachexia and in cancer patients. Further studies are required to unravel the potential role of these proteins in muscle atrophy and their interest as biomarkers of cancer cachexia.
HostingRepositoryPanoramaPublic
AnnounceDate2020-11-02
AnnouncementXMLSubmission_2020-11-02_20:16:12.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportsupported by repository but incomplete data and/or metadata
PrimarySubmitterMarie-Alice Meuwis
SpeciesList scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationListCarbamidomethyl; Oxidation; Label:13C(6)15N(2); Label:13C(6)15N(4)
InstrumentXevo TQ-S; nanoACQUITY UPLC System with 1D Technology
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-05-27 21:16:02ID requested
12020-11-02 20:10:46announced
22020-11-02 20:16:12announced: Updated citation format
Publication List
Massart IS, Paulissen G, Loumaye A, Lause P, Pötgens SA, Thibaut MM, Balan E, Deldicque L, Atfi A, Louis E, Gruson D, Bindels LB, Meuwis M-A, Thissen J-P. Marked Increased Production of Acute Phase Reactants by Skeletal Muscle during Cancer Cachexia. Cancers. 2020
12(11):3221
Keyword List
submitter keyword: Cancer, Cachexia, Skeletal muscle, Proteomics, Secretome, Acute phase reactants
Contact List
Edouard Louis
contact affiliationTranslational gastroenterology, GIGA institute, Uliege and university hospital of Liege, BE
contact emailedouard.louis@uliege.be
lab head
Marie-Alice Meuwis
contact affiliationLaboratory of translational gastroenterology, GIGA institute UNiversity of liege and university hospital of Liege, BE
contact emailmarie-alice.meuwis@uliege.be
dataset submitter
Full Dataset Link List
Panorama Public dataset URI