Trabectedin modulates macrophage polarization in the tumor-microenvironment. Role of K<inf>V</inf>1.3 and K<inf>V</inf>1.5 channels

Immune cells have an important role in the tumor-microenvironment. Macrophages may tune the immune response toward inflammatory or tolerance pathways. Tumor-associated macrophages (TAM) have a string of immunosuppressive functions and they are considered a therapeutic target in cancer. This study ai...

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Detalhes bibliográficos
Autores: Peraza, Diego A., Povo-Retana, Adrián, Mojena, Marina, García Redondo, Ana Belén, Avilés, Pablo, Boscá, Lisardo, Valenzuela, Carmen
Tipo de documento: artigo
Data de publicação:2023
País:España
Recursos:Universidad Autónoma de Madrid
Repositório:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglês
OAI Identifier:oai:repositorio.uam.es:10486/718903
Acesso em linha:http://hdl.handle.net/10486/718903
https://dx.doi.org/10.1016/j.biopha.2023.114548
Access Level:Acceso aberto
Palavra-chave:Cancer
K 1.3 V
K 1.5 V
Macrophages
TAMs
Trabectedin
Medicina
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spelling Trabectedin modulates macrophage polarization in the tumor-microenvironment. Role of K<inf>V</inf>1.3 and K<inf>V</inf>1.5 channelsPeraza, Diego A.Povo-Retana, AdriánMojena, MarinaGarcía Redondo, Ana BelénAvilés, PabloBoscá, LisardoValenzuela, CarmenCancerK 1.3 VK 1.5 VMacrophagesTAMsTrabectedinMedicinaImmune cells have an important role in the tumor-microenvironment. Macrophages may tune the immune response toward inflammatory or tolerance pathways. Tumor-associated macrophages (TAM) have a string of immunosuppressive functions and they are considered a therapeutic target in cancer. This study aimed to analyze the effects of trabectedin, an antitumor agent, on the tumor-microenvironment through the characterization of the electrophysiological and molecular phenotype of macrophages. Experiments were performed using the whole-cell configuration of the patch-clamp technique in resident peritoneal mouse macrophages. Trabectedin does not directly interact with KV1.5 and KV1.3 channels, but their treatment (16 h) with sub-cytotoxic concentrations of trabectedin increased their KV current due to an upregulation of KV1.3 channels. In vitro generated TAM (TAMiv) exhibited an M2-like phenotype. TAMiv generated a small KV current and express high levels of M2 markers. K+ current from TAMs isolated from tumors generated in mice is a mixture of KV and KCa, and in TAM isolated from tumors generated in trabectedin-treated mice, the current is mostly driven by KCa. We conclude that the antitumor capacity of trabectedin is not only due to its effects on tumor cells, but also to the modulation of the tumor microenvironment, due, at least in part, to the modulation of the expression of different macrophage ion channelsThis research was funded by AEI, Grants SAF2016-75021-R (to CV) funded by MICIN AEI/10.13039/501100011033 and by “ERDF A way of making Europe”; Grants PID2019-104366RB-C21 (to CV) and PID2020-113238RB-I00 (to L.B.) funded by MCIN/AEI/10.13039/501100011033; by CIBERCV, Grant CB/11/00222 funded by Instituto de Salud Carlos III (to LB and CV) co-financed by the European Development Regional Fund “A Way to Achieve Europe”); Comunidad de Madrid Programa Biociencias (P2022-BMD-7223); by CSIC Grants PIE201820E104 and 2019AEP148 (to CV). This research was partially funded by a grant from a PharmaMar S.A. GrantElsevierDepartamento de FisiologíaFacultad de Medicina20232023-05-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/718903https://dx.doi.org/10.1016/j.biopha.2023.114548reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7189032026-06-23T12:46:27Z
dc.title.none.fl_str_mv Trabectedin modulates macrophage polarization in the tumor-microenvironment. Role of K<inf>V</inf>1.3 and K<inf>V</inf>1.5 channels
title Trabectedin modulates macrophage polarization in the tumor-microenvironment. Role of K<inf>V</inf>1.3 and K<inf>V</inf>1.5 channels
spellingShingle Trabectedin modulates macrophage polarization in the tumor-microenvironment. Role of K<inf>V</inf>1.3 and K<inf>V</inf>1.5 channels
Peraza, Diego A.
Cancer
K 1.3 V
K 1.5 V
Macrophages
TAMs
Trabectedin
Medicina
title_short Trabectedin modulates macrophage polarization in the tumor-microenvironment. Role of K<inf>V</inf>1.3 and K<inf>V</inf>1.5 channels
title_full Trabectedin modulates macrophage polarization in the tumor-microenvironment. Role of K<inf>V</inf>1.3 and K<inf>V</inf>1.5 channels
title_fullStr Trabectedin modulates macrophage polarization in the tumor-microenvironment. Role of K<inf>V</inf>1.3 and K<inf>V</inf>1.5 channels
title_full_unstemmed Trabectedin modulates macrophage polarization in the tumor-microenvironment. Role of K<inf>V</inf>1.3 and K<inf>V</inf>1.5 channels
title_sort Trabectedin modulates macrophage polarization in the tumor-microenvironment. Role of K<inf>V</inf>1.3 and K<inf>V</inf>1.5 channels
dc.creator.none.fl_str_mv Peraza, Diego A.
Povo-Retana, Adrián
Mojena, Marina
García Redondo, Ana Belén
Avilés, Pablo
Boscá, Lisardo
Valenzuela, Carmen
author Peraza, Diego A.
author_facet Peraza, Diego A.
Povo-Retana, Adrián
Mojena, Marina
García Redondo, Ana Belén
Avilés, Pablo
Boscá, Lisardo
Valenzuela, Carmen
author_role author
author2 Povo-Retana, Adrián
Mojena, Marina
García Redondo, Ana Belén
Avilés, Pablo
Boscá, Lisardo
Valenzuela, Carmen
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Fisiología
Facultad de Medicina
dc.subject.none.fl_str_mv Cancer
K 1.3 V
K 1.5 V
Macrophages
TAMs
Trabectedin
Medicina
topic Cancer
K 1.3 V
K 1.5 V
Macrophages
TAMs
Trabectedin
Medicina
description Immune cells have an important role in the tumor-microenvironment. Macrophages may tune the immune response toward inflammatory or tolerance pathways. Tumor-associated macrophages (TAM) have a string of immunosuppressive functions and they are considered a therapeutic target in cancer. This study aimed to analyze the effects of trabectedin, an antitumor agent, on the tumor-microenvironment through the characterization of the electrophysiological and molecular phenotype of macrophages. Experiments were performed using the whole-cell configuration of the patch-clamp technique in resident peritoneal mouse macrophages. Trabectedin does not directly interact with KV1.5 and KV1.3 channels, but their treatment (16 h) with sub-cytotoxic concentrations of trabectedin increased their KV current due to an upregulation of KV1.3 channels. In vitro generated TAM (TAMiv) exhibited an M2-like phenotype. TAMiv generated a small KV current and express high levels of M2 markers. K+ current from TAMs isolated from tumors generated in mice is a mixture of KV and KCa, and in TAM isolated from tumors generated in trabectedin-treated mice, the current is mostly driven by KCa. We conclude that the antitumor capacity of trabectedin is not only due to its effects on tumor cells, but also to the modulation of the tumor microenvironment, due, at least in part, to the modulation of the expression of different macrophage ion channels
publishDate 2023
dc.date.none.fl_str_mv 2023
2023-05-01
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/10486/718903
https://dx.doi.org/10.1016/j.biopha.2023.114548
url http://hdl.handle.net/10486/718903
https://dx.doi.org/10.1016/j.biopha.2023.114548
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
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
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
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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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