PXD024852

PXD024852 is an original dataset announced via ProteomeXchange.

Title	Melanoma-derived small extracellular vesicles induce lymphangiogenesis and metastasis through a NGFR-dependent mechanism
Description	Secreted extracellular vesicles are known to influence the tumor microenvironment and promote metastasis. In this work, we have analyzed the involvement of extracellular vesicles in the establishment of lymph node pre-metastatic niches by melanoma cells. We found that small extracellular vesicles (sEVs) derived from highly metastatic melanoma cell lines spread broadly through the lymphatic system and were taken up by lymphatic endothelial cells, reinforcing lymph node metastasis. Melanoma-derived sEVs induce lymphangiogenesis, a hallmark of pre-metastatic niche formation, in vitro and in lymphoreporter mice in vivo. We found that neural growth factor receptor (NGFR) is secreted in melanoma-derived small extracellular vesicles and shuttled to lymphatic endothelial cells, inducing lymphangiogenesis and tumor cell adhesion through the activation of ERK and NF-B pathways and ICAM1 expression. Importantly, ablation or inhibition of NGFR in sEVs reversed the lymphangiogenic phenotype, decreased melanoma lymph node metastasis and extended the survival. Importantly, analysis of NGFR expression in lymph node metastases and matched primary tumors shows that levels of MITF+NGFR+ lymph node metastatic cells are correlated with disease outcome. Our data support the idea that NGFR secreted in sEVs favors lymph node pre-metastatic niche formation and lymph node metastasis in melanoma
HostingRepository	PRIDE
AnnounceDate	2021-08-05
AnnouncementXML	Submission_2021-08-05_02:35:23.090.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	henrik molina
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2021-03-19 01:54:45	ID requested
⏵ 1	2021-08-05 02:35:23	announced

Dataset with its publication pending

submitter keyword: : small extracellular vesicles, lymph Node, NGFR, pre-metastatic niche, lymphangiogenesis, melanoma, cell adhesion

Hector Peinado
contact affiliation	Microenvironment and Metastasis Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
contact email	hpeinado@cnio.es
lab head
henrik molina
contact affiliation	THE ROCKEFELLER UNIVERSITY
contact email	henrik.molina@gmail.com
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/PXD024852

PRIDE project URI

• PRIDE
  1. PXD024852
     1. Label: PRIDE project
     2. Name: Melanoma-derived small extracellular vesicles induce lymphangiogenesis and metastasis through a NGFR-dependent mechanism