PXD022635

PXD022635 is an original dataset announced via ProteomeXchange.

Title	Persistent inflammatory stimulation drives the transition of MSCs to inflammatory CAFs that promote pro-metastatic characteristics in breast cancer cells
Description	The pro-inflammatory cytokines tumor necrosis factor α (TNFα) and interleukin 1β (IL-1β) are expressed simultaneously and have tumor-promoting roles in breast cancer. In parallel, mesenchymal stem cells (MSCs) undergo transition at the tumor site to cancer-associated fibroblasts (CAFs), which are generally connected to enhanced tumor progression. Here, we determined the impact of consistent inflammatory stimulation on stromal cell plasticity. MSCs that were persistently stimulated by TNFα+IL-1β (2-3 weeks) gained a CAF-like morphology, accompanied by prominent changes in gene expression, including in stroma/fibroblast-related genes. These CAF-like cells expressed elevated levels of vimentin and fibroblast activation protein (FAP) and demonstrated significantly increased ability to contract collagen gels. Moreover, they have gained the phenotype of inflammatory CAFs, as indicated by reduced expression of α smooth muscle actin (αSMA), increased proliferation and elevated expression of inflammatory genes and proteins, primarily inflammatory chemokines. These inflammatory CAFs released factors that enhanced tumor cell detachment, spreading and migration; the inflammatory CAF-derived factors elevated cancer cell migration by stimulating the chemokine receptors CCR2, CCR5 and CXCR1/2 and Ras-activating receptors, expressed by the cancer cells. Together, these novel findings demonstrate that chronic inflammation, per se, can induce MSC-to-CAF transition, leading to generation of tumor-promoting inflammatory CAFs.
HostingRepository	PRIDE
AnnounceDate	2021-08-10
AnnouncementXML	Submission_2021-08-10_07:05:20.926.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Amir Prior
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	carbamoylated residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-11-19 06:21:45	ID requested
1	2021-08-10 01:52:22	announced
⏵ 2	2021-08-10 07:05:21	announced	2021-08-10: Updated project metadata.

Rubinstein-Achiasaf L, Morein D, Ben-Yaakov H, Liubomirski Y, Meshel T, Elbaz E, Dorot O, Pichinuk E, Gershovits M, Weil M, Ben-Baruch A, Persistent Inflammatory Stimulation Drives the Conversion of MSCs to Inflammatory CAFs That Promote Pro-Metastatic Characteristics in Breast Cancer Cells. Cancers (Basel), 13(6):(2021) [pubmed]

10.3390/CANCERS13061472;

submitter keyword: Breast cancer

Cancer-associated fibroblasts

Inflammation

Interleukin 1β

Mesenchymal stem cells

Tumor necrosis factor α.

Adit Ben-Baruch
contact affiliation	Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel
contact email	aditbb@tauex.tau.ac.il
lab head
Amir Prior
contact affiliation	Weizmann Institute of Science
contact email	amir.prior@weizmann.ac.il
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/2021/08/PXD022635

PRIDE project URI

• PRIDE
  1. PXD022635
     1. Label: PRIDE project
     2. Name: Persistent inflammatory stimulation drives the transition of MSCs to inflammatory CAFs that promote pro-metastatic characteristics in breast cancer cells