PXD019433-1

PXD019433 is an original dataset announced via ProteomeXchange.

Title	Marked increased production of acute phase reactants by skeletal muscle during cancer cachexia
Description	Background 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.
HostingRepository	PanoramaPublic
AnnounceDate	2020-11-02
AnnouncementXML	Submission_2020-11-02_20:10:40.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	supported by repository but incomplete data and/or metadata
PrimarySubmitter	Marie-Alice Meuwis
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	Carbamidomethyl; Oxidation; Label:13C(6)15N(2); Label:13C(6)15N(4)
Instrument	Xevo TQ-S; nanoACQUITY UPLC System with 1D Technology

Revision	Datetime	Status	ChangeLog Entry
0	2020-05-27 21:16:02	ID requested
⏵ 1	2020-11-02 20:10:46	announced
2	2020-11-02 20:16:12	announced	: Updated citation format
3	2021-01-24 19:55:05	announced	: Added PubMed ID

Massart, I.S.

Paulissen, G.

Loumaye, A.

Lause, P.

Pötgens, S.A.

Thibaut, M.M.

Balan, E.

Deldicque, L.

Atfi, A.

Louis, E.

Gruson, D.

Bindels, L.B.

Meuwis, M.-A.

Thissen, J.-P. Marked Increased Production of Acute Phase Reactants by Skeletal Muscle during Cancer Cachexia. Cancers 2020, 12, 3221

submitter keyword: Cancer, Cachexia, Skeletal muscle, Proteomics, Secretome, Acute phase reactants

Edouard Louis
contact affiliation	Translational gastroenterology, GIGA institute, Uliege and university hospital of Liege, BE
contact email	edouard.louis@uliege.be
lab head
Marie-Alice Meuwis
contact affiliation	Laboratory of translational gastroenterology, GIGA institute UNiversity of liege and university hospital of Liege, BE
contact email	marie-alice.meuwis@uliege.be
dataset submitter

Panorama Public dataset URI