2026-04-29T07:25:37Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/134942024-11-29T22:55:37Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
García-Silva, Susana
author
Benito-Martín, Alberto
author
Nogués, Laura
author
Hernández-Barranco, Alberto
author
Mazariegos, Marina S.
author
Santos, Vanesa
author
Hergueta-Redondo, Marta
author
Ximénez-Embún, Pilar
author
Kataru, Raghu P.
author
Lopez, Ana Amor
author
Merino, Cristina
author
Sánchez-Redondo, Sara
author
Graña-Castro, Osvaldo
author
Matei, Irina
author
Nicolás-Avila, José Ángel
author
Torres-Ruiz, Raúl
author
Rodríguez-Perales, Sandra
author
Martinez, Lola
author
Pérez-Martínez, Manuel
author
Mata, Gadea
author
Szumera-Ciećkiewicz, Anna
author
Kalinowska, Iwona
author
Saltari, Annalisa
author
Martínez-Gómez, Julia M.
author
Hogan, Sabrina A.
author
Saragovi, H. Uri
author
Ortega, Sagrario
author
Garcia-Martin, Carmen
author
Boskovic, Jasminka
author
Levesque, Mitchell P.
author
Rutkowski, Piotr
author
Hidalgo, Andres
author
Muñoz, Javier
author
Megias Vazquez, Diego
author
Mehrara, Babak J.
author
Lyden, David
author
Peinado Selgas, Hector
funder
Starr Cancer Consortium
funder
National Institutes of Health (Estados Unidos)
funder
Paduano Foundation
funder
Children s Cancer and Blood Foundation
funder
Melanoma Research Alliance
funder
Fundación Ramón Areces
funder
Fundación La Caixa
funder
Atresmedia
funder
Asociación Española Contra el Cáncer
funder
Malcolm Hewitt Wiener Foundation
funder
Fifth District AHEPA Cancer Research Foundation
funder
Hartwell Foundation
funder
Centro Nacional de Investigaciones Oncológicas Carlos III (España)
funder
Fundación AXA
funder
Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España)
funder
Manning Foundation
funder
Feldstein Foundation
funder
Translational Network for the Clinical Application of Extracellular Vesicles (TeNTaCLES)
2021-12-16T10:27:16Z
2021-12-16T10:27:16Z
2021-11-25
Nat Cancer. 2021;
http://hdl.handle.net/20.500.12105/13494
10.1038/s43018-021-00272-y
2662-1347
Nature Cancer
Secreted extracellular vesicles (EVs) influence the tumor microenvironment and promote distal metastasis. Here we analyzed the involvement of melanoma-secreted EVs in lymph node pre-metastatic niche formation in murine models. We found that small EVs (sEVs) derived from metastatic melanoma cell lines were enriched in nerve growth factor (NGF) receptor (NGFR, p75NTR), spread through the lymphatic system and were taken up by lymphatic endothelial cells, reinforcing lymph node metastasis. Remarkably, sEVs enhanced lymphangiogenesis and tumor cell adhesion by inducing ERK kinase, nuclear factor (NF)-κB activation and intracellular adhesion molecule (ICAM)-1 expression in lymphatic endothelial cells. Importantly, ablation or inhibition of NGFR in sEVs reversed the lymphangiogenic phenotype, decreased lymph node metastasis and extended survival in pre-clinical models. Furthermore, NGFR expression was augmented in human lymph node metastases relative to that in matched primary tumors, and the frequency of NGFR+ metastatic melanoma cells in lymph nodes correlated with patient survival. In summary, we found that NGFR is secreted in melanoma-derived sEVs, reinforcing lymph node pre-metastatic niche formation and metastasis.
eng
Melanoma-derived small extracellular vesicles induce lymphangiogenesis and metastasis through an NGFR-dependent mechanism
journal article
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Melanomaderivedsmallextracellular _2021.docx.txt