Use of extracellular vesicles from lymphatic drainage as surrogate markers of melanoma progression and BRAFV600E mutation

Author:

García-Silva Susana1ORCID,Benito-Martín Alberto2,Sánchez-Redondo Sara1,Hernández-Barranco Alberto1ORCID,Ximénez-Embún Pilar3,Nogués Laura1,Mazariegos Marina S.1,Brinkmann Kay4,Amor López Ana1,Meyer Lisa4,Rodríguez Carlos5,García-Martín Carmen5,Boskovic Jasminka5,Letón Rocío6,Montero Cristina6,Robledo Mercedes6,Santambrogio Laura7,Sue Brady Mary8,Szumera-Ciećkiewicz Anna9,Kalinowska Iwona10,Skog Johan11,Noerholm Mikkel4,Muñoz Javier3,Ortiz-Romero Pablo L.12,Ruano Yolanda13ORCID,Rodríguez-Peralto José L.13,Rutkowski Piotr10,Peinado Héctor1ORCID

Affiliation:

1. Microenvironment and Metastasis Laboratory, Molecular Oncology Program, Spanish National Cancer Research Center, Madrid, Spain

2. Children's Cancer and Blood Foundation Laboratories, Department of Pediatrics, Weill Cornell Medicine, New York, NY

3. Proteomics Unit–ProteoRed-Instituto de Salud Carlos III, Spanish National Cancer Research Center, Madrid, Spain

4. Exosome Diagnostics, GmbH, Martinsried, Germany

5. Electron Microscopy Unit, Spanish National Cancer Research Center, Madrid, Spain

6. Hereditary Endocrine Group, Spanish National Cancer Research Center, Madrid, Spain

7. Department of Pathology, Microbiology & Immunology, Albert Einstein College of Medicine, New York, NY

8. Memorial Sloan Kettering Cancer Center, New York, NY

9. Maria Sklodowska-Curie Institute–Oncology Center, Department of Pathology and Laboratory Medicine, Warsaw, Poland

10. Maria Sklodowska-Curie Institute–Oncology Center, Department of Soft Tissue/Bone Sarcoma and Melanoma, Warsaw, Poland

11. Exosome Diagnostics, Inc., Waltham, MA

12. Department of Dermatology, Medical school, Universidad Complutense de Madrid, Instituto i+12, Hospital Universitario 12 de Octubre, Madrid, Spain

13. Department of Pathology, Medical school, Universidad Complutense de Madrid, Instituto i+12, Hospital Universitario 12 de Octubre, Madrid, Spain

Abstract

Liquid biopsies from cancer patients have the potential to improve diagnosis and prognosis. The assessment of surrogate markers of tumor progression in circulating extracellular vesicles could be a powerful non-invasive approach in this setting. We have characterized extracellular vesicles purified from the lymphatic drainage also known as exudative seroma (ES) of stage III melanoma patients obtained after lymphadenectomy. Proteomic analysis showed that seroma-derived exosomes are enriched in proteins resembling melanoma progression. In addition, we found that the BRAFV600E mutation can be detected in ES-derived extracellular vesicles and its detection correlated with patients at risk of relapse.

Funder

National Institutes of Health

Feldstein Foundation

Starr Cancer Consortium

Ministerio de Economía y Competitividad

Ramón y Cajal Program

"La Caixa" Foundation

Fundación Científica Asociación Española Contra el Cáncer

Fundación de Investigación Oncológica

Ministerio de Economía y Competitividad-Red de Excelencia en Investigación e Innovación en Exosomas

Ramón Areces Foundation

Atresmedia-Fundación AXA

Comunidad Autónoma de Madrid

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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