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PXD028248

PXD028248 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleThe intercellular signaling network of ovarian cancer metastases
DescriptionBackground: Transcoelomic spread is the major route of metastasis of ovarian high-grade serous carcinoma (HGSC) with the omentum as the major metastatic site. Its unique tumor microenvironment with its large populations of adipocytes, mesothelial cells and immune cells establishes an intercellular signaling network that is instrumental for metastatic growth yet poorly understood. Methods: Based on transcriptomic analysis of tumor cells, tumor-associated immune and stroma cells we defined intercellular signaling pathways for 284 cytokines and growth factors and their cognate receptors after bioinformatic adjustment for contaminating cell types. The significance of individual components of this network was validated by analyzing clinical correlations and potentially pro-metastatic functions, including tumor cell migration, pro-inflammatory signal transduction and TAM expansion. Results: The data show an unexpected prominent role of host cells, and in particular of omental adipocytes, mesothelial cells and fibroblasts (CAF), in sustaining this signaling network. These cells, rather than tumor cells, are the major source of most cytokines and growth factors in the omental microenvironment (n=176 versus n=13). Many of these factors target tumor cells, are linked to metastasis and are associated with a short survival. Likewise, tumor stroma cells play a major role in both extracellular-matrix-triggered and lipid-mediated signaling. We have verified the functional significance of our observations for three exemplary instances. We show that the omental microenvironment (i) stimulates tumor cell migration via WNT4 which is highly expressed by CAF; (ii) induces pro-tumorigenic TAM proliferation in conjunction with high CSF1 expression by omental stroma cells and (iii) triggers pro-inflammatory signaling, at least in part via a HSP70 – NFkB pathway. Conclusions: The intercellular signaling network of omental metastases is majorly dependent on factors secreted by immune and stroma cells to provide an environment that supports ovarian HGSC progression. Clinically relevant pathways within this network represent novel options for therapeutic intervention.
HostingRepositoryPRIDE
AnnounceDate2021-11-25
AnnouncementXMLSubmission_2021-11-25_09:17:53.687.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJohannes Graumann
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListacetylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-09-09 07:57:23ID requested
12021-11-25 09:17:54announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: mesothelial cell, adipocyte, HSP70,ovarian carcinoma, omentum, carcinoma-associated fibroblast, WNT4, tumor microenvironment, signaling network, metastasis
Contact List
Rolf Müller
contact affiliationTranlational Oncology Group, Center for Tumor Biology and Immunology, Philipps University, Marburg, Germany
contact emailrolf.mueller@uni-marburg.de
lab head
Johannes Graumann
contact affiliationMax Planck Institute for Heart and Lung Research
contact emailjohannes.graumann@uni-marburg.de
dataset submitter
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