Melanoma-derived small extracellular vesicles induce lymphangiogenesis and metastasis by a NGFR-dependent mechanism

UID: 11345

Author(s): Ximénez-Embún, Pilar, Muñoz Peralta, Javier

Description: Description from PRIDE:

"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."

Subject of Study

Subject(s)

OncoTree Cancer Type(s)

Melanoma

Access via PRIDE

Accession #: PXD024108
Access Restrictions: Free to All
Access Instructions: All public datasets available in PRIDE Archive in the repository can be accessed via the website by FTP link, Web Service (for programmatic access), and the PRIDE Inspector stand-alone tool.
Associated Publications: García-Silva S, Benito-Martín A, Nogués L, et al. Melanoma-derived small extracellular vesicles induce lymphangiogenesis and metastasis through an NGFR-dependent mechanism. Nature Cancer. 2021; 2(12):1387-1405.
Equipment Used: LTQ Orbitrap Velos
hybrid mass spectrometer
Software Used: MaxQuant
A quantitative proteomics software package designed for analyzing large mass-spectrometric data sets. It is specifically aimed at high-resolution MS data.
Dataset Format(s): RAW
Dataset Size: 7.93 GB

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