PXD016555

PXD016555 is an original dataset announced via ProteomeXchange.

Title	Tumor-associated macrophages promote ovarian cancer cell migration by secreting transforming growth factor beta induced (TGFBI) and tenascin C
Description	A central and unique aspect of high-grade serous ovarian carcinoma (HGSC) is the extensive transcoelomic spreading of tumor cell via the peritoneal fluid or malignant ascites. We and others identified tumor-associated macrophages (TAM) in the ascites as promoters of metastasis-associated processes like extracellular matrix (ECM) remodeling, tumor cell migration, adhesion and invasion. The precise mechanisms and mediators involved in these functions of TAM are, however, largely unknown. By comparing monocyte-derived macrophages (MDM) differentiated in ascites to TAM-like asc-MDM, by LPS/IFN to inflammatory m1-MDM and by IL-10 to alternatively activated m2c-MDM, we found that conditioned media from both, asc-MDM and m2c-MDM, stimulated migration of patient-derived tumor cells, while m1-MDM failed to do so. Secretome analysis by mass spectrometry identified an overlapping set of 9 proteins secreted by both asc-MDM and m2c-MDM, but not by m1-MDM, in all tested donors. Of these, three proteins, namely transforming growth factor beta induced protein (TGFBI), tenascin C (TNC) and fibronectin (FN1), have been associated with migration-related functions. Intriguingly, increased ascites concentrations of TGFBI, TNC and fibronectin were associated with short progression-free survival. Furthermore, transcriptome and secretome analyses point to TAM as major producers of these proteins, further supporting an essential role for TAM in promoting HGSC progression. Consistent with this hypothesis, we were able to demonstrate that the migration-inducing potential of asc-MDM and m2c-MDM secretomes may be inhibited, at least partially, by neutralizing antibodies against TGFBI and TNC or siRNA-mediated silencing of TGFBI expression. In conclusion, the present study provides the first experimental evidence that TAM-derived TGFBI and TNC in ascites promote HGSC progression.
HostingRepository	PRIDE
AnnounceDate	2021-10-29
AnnouncementXML	Submission_2021-10-29_04:28:12.023.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	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-12-03 05:11:58	ID requested
1	2020-04-27 22:45:55	announced
⏵ 2	2021-10-29 04:28:12	announced	2021-10-29: Updated project metadata.

Steitz AM, Steffes A, Finkernagel F, Unger A, Sommerfeld L, Jansen JM, Wagner U, Graumann J, M, ü, ller R, Reinartz S, Tumor-associated macrophages promote ovarian cancer cell migration by secreting transforming growth factor beta induced (TGFBI) and tenascin C. Cell Death Dis, 11(4):249(2020) [pubmed]

curator keyword: Biomedical

submitter keyword: cancer, tumor-associated macrophages, ascites,high-grade serous ovarian carcinoma, tumor microenvironment

Rolf Müller
contact affiliation	Institute of Molecular Biology and Tumor Research (IMT) Center for Tumor Biology and Immunology (ZTI) Philipps-Universität Marburg
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@mpi-bn.mpg.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/04/PXD016555

PRIDE project URI

• PRIDE
  1. PXD016555
     1. Label: PRIDE project
     2. Name: Tumor-associated macrophages promote ovarian cancer cell migration by secreting transforming growth factor beta induced (TGFBI) and tenascin C