PXD028434 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Perturbation of JAK-STAT signaling in macrophages by arachidonic acid with implications for the ovarian cancer microenvironment |
Description | Progression and relapse-free survival of ovarian carcinoma are associated with the abundance of immunosuppressed CD163highCD206high tumor-associated macrophages (TAMs) and high levels of polyunsaturated fatty acids (PUFAs), in particular arachidonic acid (AA), in the tumor microenvironment. In the present study, we have investigated whether both associations are functionally linked. Methods: The effect of PUFAs on cytokine-mediated pro-inflammatory signal transduction was studied in primary monocyte-derived macrophages (MDMs) by transcriptomics, bioinformatics, phosphoprotein analysis of signal transduction proteins and MS-based proteomics of lipid rafts. Results: Pathway analysis of transcriptional profiles revealed that high CD163 and CD206/MRC1 expression in TAMs is strongly associated with an inhibition of cytokine-triggered signal transduction. This is mirrored by an impairment of the transcriptional response to interferon-beta (IFNbeta), IFNgamma and IL-6 in monocyte-derived macrophages (MDMs) by AA. This AA-mediated inhibition of pro-inflammatory signaling is caused by dysfunctions of the cognate receptors, as indicated by the inhibition by PUFAs of JAK1, JAK2, STAT1 and STAT3 phosphorylation, with the strongest inhibitory effects exerted by AA and its non-metabolizable analog ETYA. AA/ETYA treatment of MDMs results in altered composition of lipid rafts, including reduced amounts of the interferon receptor IFNAR1, STAT1 and other immune-regulatory proteins. The AA-mediated inhibition of IFN-triggered STAT1 phosphorylation was reversed by water-soluble cholesterol, known to prevent the perturbation of lipid raft structure by PUFAs. Conclusion: Our data suggest that AA, and to a lesser degree other PUFAs, impair pro-inflammatory signaling in macrophages, at least in part by altering the structure of lipid rafts, and thereby contribute to the reeducation of tumor-associated macrophages. Our findings also suggest that the pharmacologic restoration of lipid raft functions in TAM may be a promising strategy for the development of new therapeutic approaches. |
HostingRepository | PRIDE |
AnnounceDate | 2023-11-14 |
AnnouncementXML | Submission_2023-11-14_08:53:27.113.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Johannes Graumann |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2021-09-09 13:52:17 | ID requested | |
1 | 2022-08-25 11:44:10 | announced | |
⏵ 2 | 2023-11-14 08:53:28 | announced | 2023-11-14: Updated project metadata. |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Ovarian Cancer |
Arachidonic Acid |
monocyte-derived macrophages |
tumor associated macrophages |
macrophages |
JAK/STAT |
lipid rafts |
Contact List
Rolf Müller |
contact affiliation | Center for Tumor Biology and Immunology (ZTI), Philipps University, Hans-Meerwein-Strasse 3, 35043 Marburg, Germany |
contact email | rolf.mueller@uni-marburg.de |
lab head | |
Johannes Graumann |
contact affiliation | Institute of Translational Proteomics, Faculty of Medicine, Philipps-Universität Marburg |
contact email | johannes.graumann@uni-marburg.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD028434
- Label: PRIDE project
- Name: Perturbation of JAK-STAT signaling in macrophages by arachidonic acid with implications for the ovarian cancer microenvironment