PXD055261

PXD055261 is an original dataset announced via ProteomeXchange.

Title	Characterization of DNA and protein content of extracellular vesicles associated with organotropism in metastatic breast cancer
Description	While primary breast cancer (BC) is often effectively managed, metastasis remains the primary cause of BC-related fatalities. Gaps persist in our understanding of the mechanisms underlying cancer cell predilection for specific organs (organotropism). Unraveling these mediators of site-specific metastasis could enhance early detection and enable more tailored interventions. Liquid biopsy represents an innovative diagnostic approach in cancer involving the non-invasive analysis of biological materials found in body fluids like blood or urine. These materials include circulating tumor cells, cell-free circulating tumor DNA, and tumor-derived extracellular vesicles (EVs), which offer valuable insights for characterizing and monitoring tumor genomes to advance personalized medicine. EVs, lipid-bound particles released from cells into the extracellular space, facilitate intercellular communication by transporting proteins and DNA (EV-DNA) implicated in cancer progression and organ-specific metastasis. The aim of this study was to conduct an in-depth analysis of cell-free DNA (cfDNA) and EVs using a murine model of BC cell lines with distinct metastatic potentials and organotropisms (lung, bone, liver, brain). We characterized the secretome of 8 different metastatic cell lines originating from the same parental non metastatic and metastatic cell line, as well as normal mammary epithelial cells to identify unique biomarkers specific to metastatic sites. Using ultracentrifigcation, we isolated small EVs ranging from 78.9 to 101nm isolated from the conditioned media of the cell lines. We confirmed the presence of established EV markers, including CD81, TSG101 and syntenin. Transmission electron microscopy revealed interesting EV secretion patterns that differed according to cell line. We demonstrated the presence of EV-DNA and cfDNA in all the cell lines, with varying concentrations. We also found that a common BC mutation in TP53 can be specifically detected in both EV-DNA and cfDNA of cancer cell cultures using droplet digital PCR. The proteomic characterization of EVs through high throughput mass spectrometry revealed common EV signatures and proteins involved in cancer processes and organotropism unique to distinct site-specific cell lines. Specifically, we found enrichment of integrin receptors in metastatic cancer EVs compared to EVs secreted from normal epithelial cells and matched tumorigenic nonmetastatic cell lines. Gene ontology (GO) pathway analysis revealed that cancer derived EVs display a cell adhesion signature and are enriched with proteins involved in extracellular matrix interaction, focal adhesion, endocytosis, and PI3K-Akt signaling pathway. Interestingly, EVs containing heat shock proteins and DNA binding proteins are released by both cancer and normal cells. A total of 460 proteins were quantified with a high confidence level, including 70% of the TOP 200 exosome markers archived by Vesiclepedia. Taken together, we characterized the quantity and cargo of EVs in a unique model of BC organotropism, suggesting that EV-DNA and EVs were informative of normal and cancer states. This work could help to identify BC biomarkers associated with site-specific metastasis as well as new therapeutic targets.
HostingRepository	PRIDE
AnnounceDate	2025-06-02
AnnouncementXML	Submission_2025-06-01_16:23:33.618.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Amelie Nadeau
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetic acid derivatized residue; deamidated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-08-27 11:41:53	ID requested
⏵ 1	2025-06-01 16:23:34	announced

10.1186/s13046-025-03418-3;

Nadeau A, Tsering T, Abdouh M, Kienzle L, Cleyle J, Taylor L, Douanne N, Dickinson K, Siegel PM, Burnier JV, Characterization of extracellular vesicle-associated DNA and proteins derived from organotropic metastatic breast cancer cells. J Exp Clin Cancer Res, 44(1):157(2025) [pubmed]

submitter keyword: proteomics, organotropism,Extracellular vesicles, metastatic breast cancer, EV-DNA, biomarkers, cell-free DNA

Julia Valdemarin Burnier
contact affiliation	Assistant Professor, Departments of Oncology & Pathology, McGill University Principal Investigator, Cancer Research Program, MUHC-RI 1001 Decarie Blvd, EM2.2218 514.934.1934 ext 76307 Montréal, Canada
contact email	julia.burnier@mcgill.ca
lab head
Amelie Nadeau
contact affiliation	McGill University
contact email	amelie.nadeau3@mail.mcgill.ca
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/2025/06/PXD055261

PRIDE project URI

• PRIDE
  1. PXD055261
     1. Label: PRIDE project
     2. Name: Characterization of DNA and protein content of extracellular vesicles associated with organotropism in metastatic breast cancer