ArticleNature cancer2021
Melanoma-derived small extracellular vesicles induce lymphangiogenesis and metastasis through an NGFR-dependent mechanism.
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Article in Nature cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 papers, 3 of them syntheses that pooled it.
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138citing papers in PubMed, 3 pooled it
11.1field-weighted citation impact, top 1% of its field
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Who cites it
138 citing papers in PubMed, 3 syntheses or guidelines pooled it, 176 citations in OpenAlex.
- MicroRNAs and Cellular Senescence in Melanoma: An Underexplored Link to Tumor Progression-A Systematic Review with Bioinformatics Analyses.International journal of molecular sciences · 2026Pooled it
- Global hotspots and trends in pre-metastatic niche research: a bibliometric analysis(2005-2024).Frontiers in immunology · 2025Pooled it
- Predictive models for lymph node metastasis in endometrial cancer: A systematic review and bibliometric analysis.Women's health (London, England)Pooled it
- A Dual-Delivery System Designed to Overcome EV-Mediated Ferroptosis Resistance for Efficient Solid Tumor Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Role of Extracellular Vesicles in Shaping Immune Responses in the Lymph Node Microenvironment.Biology of the cell · 2026Review
- Systemic health impact of cancer-associated extracellular vesicles and particles.Nature reviews. Cancer · 2026Review
- Spatial and Single-Cell Multi-Omics Analyses of T-Cell Subsets and Interactions in Melanoma Lymph Node Metastasis.Experimental dermatology · 2026Review
- Article
- Superresolution US Imaging of Rabbit Lymph Node Microvasculature for Metastasis Diagnosis.Radiology. Imaging cancer · 2026Article
- Circulating Tumor DNA as a Biomarker for Melanoma Prognosis and Therapy.American journal of clinical dermatology · 2026Review
- Shear-Activated von Willebrand Factor Captures Extracellular Vesicles to Promote Platelet Activation and Metastasis.Journal of extracellular vesicles · 2026Article
- Extracellular vesicle-mediated GALNT1/RPRD1A glycosylation axis drives immune escape and peritoneal metastasis in gastric cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Small Extracellular Vesicle-TLN1 Modulates Gastric Cancer Cells and Remodels Lymphatic Endothelial Cells Through AKT Activation to Potentiate Lymphatic Metastasis.Cell biology international · 2026Article
- NGFR induces melanoma invasion and immunotherapy resistance through myosin light chain 2 modulation.The EMBO journal · 2026Article
- Secretion of Extracellular Vesicles Into the Mesenteric Lymph During Fasting and Lipid Absorption.Journal of extracellular biology · 2026Article
- Exosomal Oleic Acid Promotes Lymphangiogenesis and Nodal Metastasis in Cervical Cancer via the AKT/mTOR Pathway.Journal of extracellular vesicles · 2026Article
- CD133 Shapes Extracellular Vesicle Cargo and Angiogenic Function in Basal-Like Triple-Negative Breast Cancer.Journal of extracellular vesicles · 2026Article
- Circulating extracellular vesicles from early-stage lung cancer patients trigger endothelial activation to drive pre-metastatic niche formation through synergistic miR-29a and C4A signaling.Journal of experimental & clinical cancer research : CR · 2026Article
- Interventions and platforms that direct lymphangiogenesis to restore physiological homeostasis and enhance immunoregulation.NPJ Regenerative medicine · 2026Review
- Ginsenoside Rg1 Ameliorates LPS-Induced Sepsis-Associated Lung Injury in Mice via VEGFC/D-VEGFR3 Signaling-Mediated Lymphangiogenesis and Lymphatic Remodeling.The Kaohsiung journal of medical sciences · 2026Article
78 more citing papers are in PubMed but not listed here.
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Authors and funding
37 authors at 8 institutions in 5 countries.
Susana García-Silva *Microenvironment and Metastasis Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain.ORCID http://orcid.org/0000-0003-1065-0245
Alberto Benito-Martín *Children's Cancer and Blood Foundation Laboratories, Departments of Pediatrics and Cell and Developmental Biology, Weill Cornell Medical College, New York, NY, USA.
Laura NoguésMicroenvironment and Metastasis Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
Alberto Hernández-BarrancoMicroenvironment and Metastasis Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain.ORCID http://orcid.org/0000-0002-1590-5107
Marina S MazariegosMicroenvironment and Metastasis Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
Vanesa SantosMicroenvironment and Metastasis Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
Marta Hergueta-RedondoMicroenvironment and Metastasis Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
Pilar Ximénez-EmbúnProteomics Unit, ProteoRed-ISCIII, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.ORCID http://orcid.org/0000-0002-2582-9443
Raghu P KataruDepartment of Surgery, Plastic and Reconstructive Surgery Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Ana Amor LopezMicroenvironment and Metastasis Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
Cristina MerinoMicroenvironment and Metastasis Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
Sara Sánchez-RedondoMicroenvironment and Metastasis Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
Osvaldo Graña-CastroBioinformatics Unit, Structural Biology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
Irina MateiChildren's Cancer and Blood Foundation Laboratories, Departments of Pediatrics and Cell and Developmental Biology, Weill Cornell Medical College, New York, NY, USA.
José Ángel Nicolás-AvilaArea of Developmental and Cell Biology, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.ORCID http://orcid.org/0000-0002-8301-7216
Raúl Torres-RuizMolecular Cytogenetics Unit, Human Cancer Genetics Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain.ORCID http://orcid.org/0000-0001-9606-0398
Sandra Rodríguez-PeralesMolecular Cytogenetics Unit, Human Cancer Genetics Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain.ORCID http://orcid.org/0000-0001-7221-3636
Lola MartínezFlow Cytometry Unit, Biotechnology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
Manuel Pérez-MartínezCofocal Microscopy Unit, Biotechnology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain.ORCID http://orcid.org/0000-0001-8839-6895
Gadea MataCofocal Microscopy Unit, Biotechnology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
Anna Szumera-CiećkiewiczDepartment of Pathology and Laboratory Medicine, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
Iwona KalinowskaDepartment of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
Annalisa SaltariDepartment of Dermatology, University of Zurich, University of Zurich Hospital, Zurich, Switzerland.
Julia M Martínez-GómezDepartment of Dermatology, University of Zurich, University of Zurich Hospital, Zurich, Switzerland.
Sabrina A HoganDepartment of Dermatology, University of Zurich, University of Zurich Hospital, Zurich, Switzerland.ORCID http://orcid.org/0000-0003-3994-8109
H Uri SaragoviLady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada.
Sagrario OrtegaTransgenic Mice Unit, Biotechnology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
Carmen Garcia-MartinElectron Microscopy Unit, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
Jasminka BoskovicElectron Microscopy Unit, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
Mitchell P LevesqueDepartment of Dermatology, University of Zurich, University of Zurich Hospital, Zurich, Switzerland.
Piotr RutkowskiDepartment of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
Andrés HidalgoArea of Developmental and Cell Biology, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.ORCID http://orcid.org/0000-0001-5513-555X
Javier MuñozProteomics Unit, ProteoRed-ISCIII, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.ORCID http://orcid.org/0000-0003-3288-3496
Diego MegíasCofocal Microscopy Unit, Biotechnology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
Babak J MehraraDepartment of Surgery, Plastic and Reconstructive Surgery Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA. mehrarab@mskcc.org.ORCID http://orcid.org/0000-0001-5717-697X
David LydenChildren's Cancer and Blood Foundation Laboratories, Departments of Pediatrics and Cell and Developmental Biology, Weill Cornell Medical College, New York, NY, USA. dcl2001@med.cornell.edu.ORCID http://orcid.org/0000-0003-0193-4131
Héctor PeinadoMicroenvironment and Metastasis Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain. hpeinado@cnio.es.ORCID http://orcid.org/0000-0002-4256-3413
Spanish National Cancer Research Centre · ESUniversity of Zurich · CHCornell University · USMemorial Sloan Kettering Cancer Center · USSpanish National Centre for Cardiovascular Research · ESThe Maria Sklodowska-Curie National Research Institute of Oncology · PLInstytut Hematologii i Transfuzjologi · PLJewish General Hospital · CA
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4MMechanisms of fibrosis in post-surgical lymphedemaR01HL111130 · NHLBI · SLOAN-KETTERING INST CAN RESEARCH · PI MEHRARA, BABAK J · 2012 to 2021
$7.2MSystemic regulation of metastasisR35CA232093 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI LYDEN, DAVID CHARLES · 2018 to 2024
$7.0MExosome-mediated Transfer of c-MET to Bone Marrow Progenitors Promotes MetastasisR01CA169416 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI LYDEN, DAVID CHARLES, PEINADO, HECTOR · 2013 to 2017
$1.7MNCI NIH HHS P30 CA008748NCI NIH HHS R01 CA169416NCI NIH HHS R35 CA232093NHLBI NIH HHS R01 HL111130
Abstract
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 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
Indexed as
Extracellular VesiclesMelanomaAnimalsEndothelial CellsHumansLymphangiogenesisLymphatic MetastasisMiceNerve Tissue ProteinsReceptors, Nerve Growth FactorTumor MicroenvironmentNerve Tissue ProteinsNGFR protein, humanReceptors, Nerve Growth FactorCD271cell adhesionlymphangiogenesislymph node metastasismelanoma metastasismetastasis mechanismsNGFRp75NTRpre-metastatic niche formationsmall extracellular vesicles
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