PXD005539

PXD005539 is an original dataset announced via ProteomeXchange.

Title	Human melanoma-derived extracellular vesicles reprogram dendritic cells potentially enabling lymph node metastases
Description	Evolution of melanoma from a primary tumor to widespread metastasis is crucially dependent on lymphatic spread. The mechanisms regulating the initial step in metastatic dissemination via regional lymph nodes remain largely unknown. We have previously described a dysfunctional immune profile that precedes evidence of metastasis in the first node draining from the primary tumor, the sentinel lymph node (SLN). Herein, we explore the role of melanoma-derived extracellular vesicles (EVs) as mediators of this pre-metastatic niche through cargo-specific polarization of dendritic cells (DCs). Utilizing mass cytometry, pre-metastatic SLNs demonstrate compromised co-stimulatory CD80 expression compared to healthy lymph nodes. Similarly, DCs matured in vitro in the presence of melanoma EVs showed impaired co-stimulation and polarization towards a chronic inflammatory cytokine milieu. Profiling of melanoma EV cargo identified shared proteomic and RNA signatures including the signaling axis S100A8, S100A9 and cognate receptor TLR4. Mechanistically, S100A8 and S100A9 compromised DC maturation, a phenotype which was partially recovered following TLR4 blockade. Early evidence demonstrates similar EVs can be isolated from human afferent lymphatic fluid ex vivo. Taken together, we propose synergistic interactions among melanoma EV cargo are responsible for suppressing DC maturation, potentially explaining the survival of malignant melanocytes metastasizing into seemingly “normal” regional lymph nodes.
HostingRepository	PRIDE
AnnounceDate	2018-10-26
AnnouncementXML	Submission_2018-10-26_12:17:47.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD005539
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Benjamin Madden
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	Ammonia-loss; Dehydrated; Oxidation; Acetyl; Carbamidomethyl
Instrument	Q Exactive; LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2016-12-09 08:42:06	ID requested
⏵ 1	2018-10-26 12:17:48	announced

Maus RLG, Jakub JW, Nevala WK, Christensen TA, Noble-Orcutt K, Sachs Z, Hieken TJ, Markovic SN, Human Melanoma-Derived Extracellular Vesicles Regulate Dendritic Cell Maturation. Front Immunol, 8():358(2017) [pubmed]

curator keyword: Biomedical

submitter keyword: Extracellular vesicles1, Dendritic cells2, Lymphatics3, Metastasis4, Tumor Immunology5

Svetomir N Markovic
contact affiliation	Consultant Medical oncology
contact email	markovic.svetomir@mayo.edu
lab head
Benjamin Madden
contact affiliation	Mayo Clinic
contact email	madden.benjamin@mayo.edu
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/2018/10/PXD005539

PRIDE project URI

• PRIDE
  1. PXD005539
     1. Label: PRIDE project
     2. Name: Human melanoma-derived extracellular vesicles reprogram dendritic cells potentially enabling lymph node metastases