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

Susana García-Silva; Alberto Benito-Martín; Sara Sánchez-Redondo; Alberto Hernández-Barranco; Pilar Ximénez-Embún; Laura Nogués; Marina S. Mazariegos; Kay Brinkmann; Ana Amor López; Lisa Meyer; Carlos Rodríguez; Carmen García-Martín; Jasminka Boskovic; Rocío Letón; Cristina Montero; Mercedes Robledo; Laura Santambrogio; Mary Sue Brady; Anna Szumera-Ciećkiewicz; Iwona Kalinowska; Johan Skog; Mikkel Noerholm; Javier Muñoz; Pablo L. Ortiz-Romero; Yolanda Ruano; José L. Rodríguez-Peralto; Piotr Rutkowski; Héctor Peinado

doi:10.1084/jem.20181522

Use of extracellular vesicles from lymphatic drainage as surrogate markers of melanoma progression and BRAF^V600E mutation

Susana García-Silva, Alberto Benito-Martín, Sara Sánchez-Redondo, Alberto Hernández-Barranco, Pilar Ximénez-Embún, Laura Nogués, Marina S. Mazariegos, Kay Brinkmann, Ana Amor López, Lisa Meyer, Carlos Rodríguez, Carmen García-Martín, Jasminka Boskovic, Rocío Letón, Cristina Montero, Mercedes Robledo, Laura Santambrogio, Mary Sue Brady, Anna Szumera-Ciećkiewicz, Iwona KalinowskaJohan Skog, Mikkel Noerholm, Javier Muñoz, Pablo L. Ortiz-Romero, Yolanda Ruano, José L. Rodríguez-Peralto, Piotr Rutkowski, Héctor Peinado

Pathology

Research output: Contribution to journal › Article › peer-review

73 Scopus citations

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 BRAF^V600E mutation can be detected in ES-derived extracellular vesicles and its detection correlated with patients at risk of relapse.

Original language	English (US)
Pages (from-to)	1061-1070
Number of pages	10
Journal	Journal of Experimental Medicine
Volume	216
Issue number	5
DOIs	https://doi.org/10.1084/jem.20181522
State	Published - May 1 2019

ASJC Scopus subject areas

Medicine(all)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1084/jem.20181522

Cite this

García-Silva, S., Benito-Martín, A., Sánchez-Redondo, S., Hernández-Barranco, A., Ximénez-Embún, P., Nogués, L., Mazariegos, M. S., Brinkmann, K., López, A. A., Meyer, L., Rodríguez, C., García-Martín, C., Boskovic, J., Letón, R., Montero, C., Robledo, M., Santambrogio, L., Brady, M. S., Szumera-Ciećkiewicz, A., ... Peinado, H. (2019). Use of extracellular vesicles from lymphatic drainage as surrogate markers of melanoma progression and BRAF^V600E mutation. Journal of Experimental Medicine, 216(5), 1061-1070. https://doi.org/10.1084/jem.20181522

García-Silva, S, Benito-Martín, A, Sánchez-Redondo, S, Hernández-Barranco, A, Ximénez-Embún, P, Nogués, L, Mazariegos, MS, Brinkmann, K, López, AA, Meyer, L, Rodríguez, C, García-Martín, C, Boskovic, J, Letón, R, Montero, C, Robledo, M, Santambrogio, L, Brady, MS, Szumera-Ciećkiewicz, A, Kalinowska, I, Skog, J, Noerholm, M, Muñoz, J, Ortiz-Romero, PL, Ruano, Y, Rodríguez-Peralto, JL, Rutkowski, P & Peinado, H 2019, 'Use of extracellular vesicles from lymphatic drainage as surrogate markers of melanoma progression and BRAF^V600E mutation', Journal of Experimental Medicine, vol. 216, no. 5, pp. 1061-1070. https://doi.org/10.1084/jem.20181522

@article{07ae0d529c3e495b9808d0a432000455,

title = "Use of extracellular vesicles from lymphatic drainage as surrogate markers of melanoma progression and BRAFV600E mutation",

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.",

author = "Susana Garc{\'i}a-Silva and Alberto Benito-Mart{\'i}n and Sara S{\'a}nchez-Redondo and Alberto Hern{\'a}ndez-Barranco and Pilar Xim{\'e}nez-Emb{\'u}n and Laura Nogu{\'e}s and Mazariegos, {Marina S.} and Kay Brinkmann and L{\'o}pez, {Ana Amor} and Lisa Meyer and Carlos Rodr{\'i}guez and Carmen Garc{\'i}a-Mart{\'i}n and Jasminka Boskovic and Roc{\'i}o Let{\'o}n and Cristina Montero and Mercedes Robledo and Laura Santambrogio and Brady, {Mary Sue} and Anna Szumera-Cie{\'c}kiewicz and Iwona Kalinowska and Johan Skog and Mikkel Noerholm and Javier Mu{\~n}oz and Ortiz-Romero, {Pablo L.} and Yolanda Ruano and Rodr{\'i}guez-Peralto, {Jos{\'e} L.} and Piotr Rutkowski and H{\'e}ctor Peinado",

note = "Funding Information: This work was supported by the US National Institutes of Health (R01-CA169416), the Feldstein Foundation, the Starr Cancer Consortium, Ministerio de Econom{\'i}a y Competitividad, the Ram{\'o}n y Cajal Program, Atresmedia-Fundaci{\'o}n AXA, {"}La Caixa{"} Foundation (ID 100010434, Fellowship LCF/BQ/ES17/ 11600007), Fundaci{\'o}n Cient{\'i}fica Asociaci{\'o}n Espa{\~n}ola Contra el C{\'a}ncer, Fundaci{\'o}n de Investigaci{\'o}n Oncol{\'o}gica, Ministerio de Econom{\'i}a y Competitividad-Red de Excelencia en Investigaci{\'o}n e Innovaci{\'o}n en Exosomas, the Ram{\'o}n Areces Foundation, and Comunidad Aut{\'o}noma de Madrid. Funding Information: We thank the members of Dr. H. Peinado{\textquoteright}s, Dr. M. Soengas{\textquoteright}, Dr. M. Ya{\~n}ez-Mo{\textquoteright}s, and Dr. D. Lyden{\textquoteright}s laboratories for reagents and discussions. This work was supported by the US National Institutes of Health (R01-CA169416), the Feldstein Foundation, the Starr Cancer Consortium, Ministerio de Econom{\'i}a y Competitividad, the Ram{\'o}n y Cajal Program, Atresmedia-Fundaci{\'o}n AXA, {"}La Caixa{"} Foundation (ID 100010434, Fellowship LCF/BQ/ES17/11600007), Fundaci{\'o}n Cient{\'i}fica Asociaci{\'o}n Espa{\~n}ola Contra el C{\'a}ncer, Fundaci{\'o}n de Investigaci{\'o}n Oncol{\'o}gica, Ministerio de Econom{\'i}a y Competitividad-Red de Excelencia en Investigaci{\'o}n e Innovaci{\'o}n en Exosomas, the Ram{\'o}n Areces Foundation, and Comunidad Aut{\'o}noma de Madrid. K. Brinkmann, L. Meyer, J. Skog, and M. Noerholm are employees of Exosome Diagnostics. P. Rutkowski has served as a member of the Advisory Board for Novartis, Amgen, Merck Sharp & Dohme, Roche, Bristol-Myers Squibb, Bayer, and Blueprint Medicine and has received honoraria for lectures from Novartis, Pfizer, Merck Sharp & Dohme, Bristol-Myers Squibb, and Roche. Publisher Copyright: {\textcopyright} 2019 Garc{\'i}a-Silva et al.",

year = "2019",

month = may,

day = "1",

doi = "10.1084/jem.20181522",

language = "English (US)",

volume = "216",

pages = "1061--1070",

journal = "Journal of Experimental Medicine",

issn = "0022-1007",

publisher = "Rockefeller University Press",

number = "5",

}

TY - JOUR

T1 - Use of extracellular vesicles from lymphatic drainage as surrogate markers of melanoma progression and BRAFV600E mutation

AU - García-Silva, Susana

AU - Benito-Martín, Alberto

AU - Sánchez-Redondo, Sara

AU - Hernández-Barranco, Alberto

AU - Ximénez-Embún, Pilar

AU - Nogués, Laura

AU - Mazariegos, Marina S.

AU - Brinkmann, Kay

AU - López, Ana Amor

AU - Meyer, Lisa

AU - Rodríguez, Carlos

AU - García-Martín, Carmen

AU - Boskovic, Jasminka

AU - Letón, Rocío

AU - Montero, Cristina

AU - Robledo, Mercedes

AU - Santambrogio, Laura

AU - Brady, Mary Sue

AU - Szumera-Ciećkiewicz, Anna

AU - Kalinowska, Iwona

AU - Skog, Johan

AU - Noerholm, Mikkel

AU - Muñoz, Javier

AU - Ortiz-Romero, Pablo L.

AU - Ruano, Yolanda

AU - Rodríguez-Peralto, José L.

AU - Rutkowski, Piotr

AU - Peinado, Héctor

N1 - Funding Information: This work was supported by the US National Institutes of Health (R01-CA169416), the Feldstein Foundation, the Starr Cancer Consortium, Ministerio de Economía y Competitividad, the Ramón y Cajal Program, Atresmedia-Fundación AXA, "La Caixa" Foundation (ID 100010434, Fellowship LCF/BQ/ES17/ 11600007), 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, the Ramón Areces Foundation, and Comunidad Autónoma de Madrid. Funding Information: We thank the members of Dr. H. Peinado’s, Dr. M. Soengas’, Dr. M. Yañez-Mo’s, and Dr. D. Lyden’s laboratories for reagents and discussions. This work was supported by the US National Institutes of Health (R01-CA169416), the Feldstein Foundation, the Starr Cancer Consortium, Ministerio de Economía y Competitividad, the Ramón y Cajal Program, Atresmedia-Fundación AXA, "La Caixa" Foundation (ID 100010434, Fellowship LCF/BQ/ES17/11600007), 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, the Ramón Areces Foundation, and Comunidad Autónoma de Madrid. K. Brinkmann, L. Meyer, J. Skog, and M. Noerholm are employees of Exosome Diagnostics. P. Rutkowski has served as a member of the Advisory Board for Novartis, Amgen, Merck Sharp & Dohme, Roche, Bristol-Myers Squibb, Bayer, and Blueprint Medicine and has received honoraria for lectures from Novartis, Pfizer, Merck Sharp & Dohme, Bristol-Myers Squibb, and Roche. Publisher Copyright: © 2019 García-Silva et al.

PY - 2019/5/1

Y1 - 2019/5/1

N2 - 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.

AB - 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.

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