PXD024108-1

PXD024108 is an original dataset announced via ProteomeXchange.

Title	Melanoma-derived small extracellular vesicles induce lymphangiogenesis and metastasis by 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 establishing the lymph node pre-metastatic niche by melanoma cells. We found that small extracellular vesicles (sEVs) derived from highly metastatic melanoma cell lines spread broadly through the lymphatic system and are 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. Analysis of involved factors demonstrated that the 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 mice 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 that NGFR is secreted in sEVs favoring lymph node pre-metastatic niche formation and lymph node metastasis in melanoma.
HostingRepository	PRIDE
AnnounceDate	2021-07-16
AnnouncementXML	Submission_2021-07-15_23:26:38.769.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Pilar Ximenez-Embun
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2021-02-10 04:12:50	ID requested
⏵ 1	2021-07-15 23:26:39	announced

Dataset with its publication pending

submitter keyword: exosomes, NGFR,Mouse, metastatic melanoma

Javier Muñoz Peralta
contact affiliation	Spanish National Cancer Research Centre (CNIO) Address: Melchor Fernández Almagro, 3. 28029 Madrid. SPAIN
contact email	jmunozpe@cnio.es
lab head
Pilar Ximenez-Embun
contact affiliation	Proteomics Group
contact email	mpximenez@cnio.es
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD024108
     1. Label: PRIDE project
     2. Name: Melanoma-derived small extracellular vesicles induce lymphangiogenesis and metastasis by a NGFR-dependent mechanism