ALK-fusion transcripts can be detected in extracellular vesicles (EVs) from nonsmall cell lung cancer cell lines and patient plasma: Toward EV-based noninvasive testing

Artículo escrito por un elevado número de autores, sólo se referencian el que aparece en primer lugar y los autores pertenecientes a la UAM

Detalles Bibliográficos
Autores: Sánchez Herrero, Estela, Provencio Pulla, Mariano
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/711467
Acceso en línea:http://hdl.handle.net/10486/711467
https://dx.doi.org/10.1093/clinchem/hvac021
Access Level:acceso abierto
Palabra clave:ALK-TKI
EML4-ALK
extracellular vesicles
liquid biopsy
NSCLC
Medicina
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spelling ALK-fusion transcripts can be detected in extracellular vesicles (EVs) from nonsmall cell lung cancer cell lines and patient plasma: Toward EV-based noninvasive testingSánchez Herrero, EstelaProvencio Pulla, MarianoALK-TKIEML4-ALKextracellular vesiclesliquid biopsyNSCLCMedicinaArtículo escrito por un elevado número de autores, sólo se referencian el que aparece en primer lugar y los autores pertenecientes a la UAMALK rearrangements are present in 5% of nonsmall cell lung cancer (NSCLC) tumors and identify patients who can benefit from ALK inhibitors. ALK fusions testing using liquid biopsies, although challenging, can expand the therapeutic options for ALK-positive NSCLC patients considerably. RNA inside extracellular vesicles (EVs) is protected from RNases and other environmental factors, constituting a promising source for noninvasive fusion transcript detection. EVs from H3122 and H2228 cell lines, harboring EML4-ALK variant 1 (E13; A20) and variant 3 (E6a/b; A20), respectively, were successfully isolated by sequential centrifugation of cell culture supernatants. EVs were also isolated from plasma samples of 16 ALK-positive NSCLC patients collected before treatment initiation. Purified EVs from cell cultures were characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and flow cytometry. Western blot and confocal microscopy confirmed the expression of EV-specific markers as well as the expression of EML4-ALK-fusion proteins in EV fractions from H3122 and H2228 cell lines. In addition, RNA from EV fractions derived from cell culture was analyzed by digital PCR (dPCR) and ALK-fusion transcripts were clearly detected. Similarly, plasma-derived EVs were characterized by NTA, flow cytometry, and the ExoView platform, the last showing that EV-specific markers captured EV populations containing ALK-fusion protein. Finally, ALK fusions were identified in 50% (8/16) of plasma EV-enriched fractions by dPCR, confirming the presence of fusion transcripts in EV fractions. ALK-fusion transcripts can be detected in EV-enriched fractions. These results set the stage for the development of EV-based noninvasive ALK testingThis study has been funded by Instituto de Salud Carlos III through the project “PI17/01977” (co-funded by European Regional Development Fund/European Social Fund “A way to make Europe”/“Investing in your future”). The work presented in this paper also received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 875160. E. Sa´nchezHerrero was funded by the Consejerıa de Ciencia, Universidades e Innovacio´n of the Comunidad de Madrid (Doctorados Industriales of the Comunidad de Madrid IND2019/BMD-17258). R. Serna-Blasco was funded by the Consejerıa de Educacio´n, Juventud y Deporte of the Comunidad de Madrid and by the Fondo Social Europeo (Programa Operativo de Empleo Juvenil, and Iniciativa de Empleo Juvenil, PEJD2018-PRE/BMD-8640). M. Vales-Go´mez was funded by Spanish Ministry of Science and Innovation (MCIU/AEI/FEDER, EU) grant RTI2018-093569-B-I00 and Madrid Regional Government under grant “IMMUNOTHERCAN” (S2017/BMD-3733-2). This work was supported by GEIVEX, Network of Excellence in the Research and Innovation on Exosomes REDIEX, SAF2015-71231-REDT, Network of Excellence in Translational NeTwork for the CLinical application of Extracellular VesicleS (TeNTaCLES) (RED2018-102411-T). M. Provencio, grants from BristolMyers Squibb, Roche, and AstraZenecaOxford University PressDepartamento de MedicinaFacultad de Medicina20222022-03-28research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/711467https://dx.doi.org/10.1093/clinchem/hvac021reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7114672026-06-23T12:46:27Z
dc.title.none.fl_str_mv ALK-fusion transcripts can be detected in extracellular vesicles (EVs) from nonsmall cell lung cancer cell lines and patient plasma: Toward EV-based noninvasive testing
title ALK-fusion transcripts can be detected in extracellular vesicles (EVs) from nonsmall cell lung cancer cell lines and patient plasma: Toward EV-based noninvasive testing
spellingShingle ALK-fusion transcripts can be detected in extracellular vesicles (EVs) from nonsmall cell lung cancer cell lines and patient plasma: Toward EV-based noninvasive testing
Sánchez Herrero, Estela
ALK-TKI
EML4-ALK
extracellular vesicles
liquid biopsy
NSCLC
Medicina
title_short ALK-fusion transcripts can be detected in extracellular vesicles (EVs) from nonsmall cell lung cancer cell lines and patient plasma: Toward EV-based noninvasive testing
title_full ALK-fusion transcripts can be detected in extracellular vesicles (EVs) from nonsmall cell lung cancer cell lines and patient plasma: Toward EV-based noninvasive testing
title_fullStr ALK-fusion transcripts can be detected in extracellular vesicles (EVs) from nonsmall cell lung cancer cell lines and patient plasma: Toward EV-based noninvasive testing
title_full_unstemmed ALK-fusion transcripts can be detected in extracellular vesicles (EVs) from nonsmall cell lung cancer cell lines and patient plasma: Toward EV-based noninvasive testing
title_sort ALK-fusion transcripts can be detected in extracellular vesicles (EVs) from nonsmall cell lung cancer cell lines and patient plasma: Toward EV-based noninvasive testing
dc.creator.none.fl_str_mv Sánchez Herrero, Estela
Provencio Pulla, Mariano
author Sánchez Herrero, Estela
author_facet Sánchez Herrero, Estela
Provencio Pulla, Mariano
author_role author
author2 Provencio Pulla, Mariano
author2_role author
dc.contributor.none.fl_str_mv Departamento de Medicina
Facultad de Medicina
dc.subject.none.fl_str_mv ALK-TKI
EML4-ALK
extracellular vesicles
liquid biopsy
NSCLC
Medicina
topic ALK-TKI
EML4-ALK
extracellular vesicles
liquid biopsy
NSCLC
Medicina
description Artículo escrito por un elevado número de autores, sólo se referencian el que aparece en primer lugar y los autores pertenecientes a la UAM
publishDate 2022
dc.date.none.fl_str_mv 2022
2022-03-28
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/711467
https://dx.doi.org/10.1093/clinchem/hvac021
url http://hdl.handle.net/10486/711467
https://dx.doi.org/10.1093/clinchem/hvac021
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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