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PXD024108

PXD024108 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMelanoma-derived small extracellular vesicles induce lymphangiogenesis and metastasis by a NGFR-dependent mechanism
DescriptionSecreted 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.
HostingRepositoryPRIDE
AnnounceDate2021-07-16
AnnouncementXMLSubmission_2021-07-15_23:26:38.769.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterPilar Ximenez-Embun
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentLTQ Orbitrap Velos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-02-10 04:12:50ID requested
12021-07-15 23:26:39announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: exosomes, NGFR,Mouse, metastatic melanoma
Contact List
Javier Muñoz Peralta
contact affiliationSpanish National Cancer Research Centre (CNIO) Address: Melchor Fernández Almagro, 3. 28029 Madrid. SPAIN
contact emailjmunozpe@cnio.es
lab head
Pilar Ximenez-Embun
contact affiliationProteomics Group
contact emailmpximenez@cnio.es
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
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