PXD061656

PXD061656 is an original dataset announced via ProteomeXchange.

Title	Extracellular vesicles from TGF-β-activated cancer-associated fibroblasts remodel the tumor microenvironment through EV surface-associated proteins
Description	Cancer-associated fibroblasts (CAFs) are a major stromal cell type within the tumor microenvironment (TME). Transforming growth factor-β (TGF-β) is a key cytokine in the TME that activates CAFs, which alters their ability to remodel the extracellular matrix (ECM) and changes their secretome profile. However, the effects of TGF-β-activated CAF-derived extracellular vesicles (EVs) on the TME, and how TGF-β-induced CAF activation influences the composition of EV cargo and remodels the TME remain largely unexplored. In this study, we reveal the altered protein composition and function of EVs derived from TGF-β-activated CAFs compared to those derived from non-activated CAF-derived EVs. Notably, several proteins that are significantly upregulated in TGF-β-activated CAF-derived EVs (TGF-β-EVs) are found on the surface of these EVs. One such protein is tumor necrosis factor-stimulated gene-6 protein (TSG6), which interacts with its receptor CD44 on the EVs and hyaluronan. These surface-associated proteins facilitate the docking of EVs to cell membrane by binding to transmembrane cell surface receptors. The elevated TSG6 on EV surface promotes the clustering of the co-receptor CD44, and TGF-β type I receptor (TGFBR1) on recipient cells, and thereby enhancing TGF-β receptor signaling. Consequently, TGF-β-EVs further activate CAFs and contribute to the immunosuppression of CD8+ T cells, which facilitates cancer progression. Overall, our findings reveal the effect of CAF-derived EVs on other cell types in TME in a contact-dependent manner, and suggest a potential universal mechanism by which EV surface-associated proteins regulate cell signaling by interacting with and clustering cell receptors, particularly in cells with low EV uptake.
HostingRepository	PRIDE
AnnounceDate	2026-02-23
AnnouncementXML	Submission_2026-02-22_16:43:52.167.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Rayman Tjokrodirijo
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-10 09:20:10	ID requested
⏵ 1	2026-02-22 16:43:53	announced

Li C, Enciso-Martinez A, Zhu L, Rotman SA, van Veelen PA, Koning RI, Mei H, Ten Dijke P, Signaling in a Contact-Dependent Manner. Adv Sci (Weinh), 13(8):e13286(2026) [pubmed]

10.1002/advs.202513286;

submitter keyword: Cancer-associated fibroblast, TGF-β, TSG6, CD8+ T cells, extracellular vesicles, EV surface-associated proteins

Peter A. van Veelen
contact affiliation	Head Proteomics Group, Leiden University Medical Center, Center for Proteomics and Metabolomics, PO Box 9600, Postal zone P1-Q, 2300 RC Leiden, The Netherlands
contact email	P.A.van_Veelen@lumc.nl
lab head
Rayman Tjokrodirijo
contact affiliation	Leiden University Medical Center, Proteomics group
contact email	r.t.n.tjokrodirijo@lumc.nl
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/2026/02/PXD061656

PRIDE project URI

• PRIDE
  1. PXD061656
     1. Label: PRIDE project
     2. Name: Extracellular vesicles from TGF-β-activated cancer-associated fibroblasts remodel the tumor microenvironment through EV surface-associated proteins