PXD028248-1

PXD028248 is an original dataset announced via ProteomeXchange.

Title	The intercellular signaling network of ovarian cancer metastases
Description	Background: 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.
HostingRepository	PRIDE
AnnounceDate	2021-11-25
AnnouncementXML	Submission_2021-11-25_09:17:53.687.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; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-09-09 07:57:23	ID requested
⏵ 1	2021-11-25 09:17:54	announced
2	2021-12-15 08:05:37	announced	2021-12-15: Updated publication reference for PubMed record(s): 34841720.

Dataset with its publication pending

submitter keyword: mesothelial cell, adipocyte, HSP70,ovarian carcinoma, omentum, carcinoma-associated fibroblast, WNT4, tumor microenvironment, signaling network, metastasis

Rolf Müller
contact affiliation	Tranlational Oncology Group, Center for Tumor Biology and Immunology, Philipps University, Marburg, Germany
contact email	rolf.mueller@uni-marburg.de
lab head
Johannes Graumann
contact affiliation	Max Planck Institute for Heart and Lung Research
contact email	johannes.graumann@uni-marburg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD028248
     1. Label: PRIDE project
     2. Name: The intercellular signaling network of ovarian cancer metastases