Telomerase deficiency and dysfunctional telomeres in the lung tumor microenvironment impair tumor progression in NSCLC mouse models and patient-derived xenografts.

Non-small cell lung cancer (NSCLC) is a leading cause of cancer death. Tumor progression depends on interactions of cancer cells with the tumor microenvironment. Here, we find increased copy number and mRNA expression of the catalytic subunit of telomerase, TERT, in tumors from NSCLC patients, contr...

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Autores: Piñeiro-Hermida, Sergio, Bosso, Giuseppe, Sánchez-Vázquez, Raúl, Martínez, Paula, Blasco, MA
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/18977
Acceso en línea:http://hdl.handle.net/20.500.12105/18977
Access Level:acceso abierto
Palabra clave:Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Telomerase
Humans
Mice
Animals
Heterografts
Tumor Microenvironment
Telomere
Lung
Cell Line, Tumor
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spelling Telomerase deficiency and dysfunctional telomeres in the lung tumor microenvironment impair tumor progression in NSCLC mouse models and patient-derived xenografts.Piñeiro-Hermida, SergioBosso, GiuseppeSánchez-Vázquez, RaúlMartínez, PaulaBlasco, MACarcinoma, Non-Small-Cell LungLung NeoplasmsTelomeraseHumansMiceAnimalsHeterograftsTumor MicroenvironmentTelomereLungCell Line, TumorNon-small cell lung cancer (NSCLC) is a leading cause of cancer death. Tumor progression depends on interactions of cancer cells with the tumor microenvironment. Here, we find increased copy number and mRNA expression of the catalytic subunit of telomerase, TERT, in tumors from NSCLC patients, contributing to a lower survival. Moreover, TERT expression in NSCLC patients from the TCGA cohort is mainly associated to the reduced infiltration of CD8+ T lymphocytes, as well as to increased infiltration of myeloid-derived suppressor cells (MDSCs). We also show that TERT deficiency and dysfunctional telomeres induced by 6-thio-dG treatment in mice reduced lung tumor implantation and vascularization, increased DNA damage response, cell cycle arrest and apoptosis, as well as reduced proliferation, inflammation, lung tumor immunosupression and invasion upon induction of a Lewis lung carcinoma (LLC). Furthermore, 6-thio-dG-treated human NSCLC xenografts exhibited increased telomere damage, cell cycle arrest and apoptosis, as well as reduced proliferation, resulting in a reduced tumor growth. Our results show that targeting telomeres might be an effective therapeutic strategy in NSCLC.Nature Publishing GroupUnión Europea. Comisión Europea. European Research Council (ERC)Asociación Española Contra el CáncerInstituto de Salud Carlos IIIFundación Banco SantanderAgencia Estatal de Investigación (España)Fundación La Caixa20242024-03-1820232023-06-0120232023-06-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfapplication/vnd.openxmlformats-officedocument.wordprocessingml.documentapplication/pdfhttp://hdl.handle.net/20.500.12105/18977reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)InglésengEuropean Commission http://dx.doi.org/10.13039/501100000780 Horizon 2020 Framework Programme 882385open accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/189772026-06-12T12:43:37Z
dc.title.none.fl_str_mv Telomerase deficiency and dysfunctional telomeres in the lung tumor microenvironment impair tumor progression in NSCLC mouse models and patient-derived xenografts.
title Telomerase deficiency and dysfunctional telomeres in the lung tumor microenvironment impair tumor progression in NSCLC mouse models and patient-derived xenografts.
spellingShingle Telomerase deficiency and dysfunctional telomeres in the lung tumor microenvironment impair tumor progression in NSCLC mouse models and patient-derived xenografts.
Piñeiro-Hermida, Sergio
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Telomerase
Humans
Mice
Animals
Heterografts
Tumor Microenvironment
Telomere
Lung
Cell Line, Tumor
title_short Telomerase deficiency and dysfunctional telomeres in the lung tumor microenvironment impair tumor progression in NSCLC mouse models and patient-derived xenografts.
title_full Telomerase deficiency and dysfunctional telomeres in the lung tumor microenvironment impair tumor progression in NSCLC mouse models and patient-derived xenografts.
title_fullStr Telomerase deficiency and dysfunctional telomeres in the lung tumor microenvironment impair tumor progression in NSCLC mouse models and patient-derived xenografts.
title_full_unstemmed Telomerase deficiency and dysfunctional telomeres in the lung tumor microenvironment impair tumor progression in NSCLC mouse models and patient-derived xenografts.
title_sort Telomerase deficiency and dysfunctional telomeres in the lung tumor microenvironment impair tumor progression in NSCLC mouse models and patient-derived xenografts.
dc.creator.none.fl_str_mv Piñeiro-Hermida, Sergio
Bosso, Giuseppe
Sánchez-Vázquez, Raúl
Martínez, Paula
Blasco, MA
author Piñeiro-Hermida, Sergio
author_facet Piñeiro-Hermida, Sergio
Bosso, Giuseppe
Sánchez-Vázquez, Raúl
Martínez, Paula
Blasco, MA
author_role author
author2 Bosso, Giuseppe
Sánchez-Vázquez, Raúl
Martínez, Paula
Blasco, MA
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Unión Europea. Comisión Europea. European Research Council (ERC)
Asociación Española Contra el Cáncer
Instituto de Salud Carlos III
Fundación Banco Santander
Agencia Estatal de Investigación (España)
Fundación La Caixa
dc.subject.none.fl_str_mv Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Telomerase
Humans
Mice
Animals
Heterografts
Tumor Microenvironment
Telomere
Lung
Cell Line, Tumor
topic Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Telomerase
Humans
Mice
Animals
Heterografts
Tumor Microenvironment
Telomere
Lung
Cell Line, Tumor
description Non-small cell lung cancer (NSCLC) is a leading cause of cancer death. Tumor progression depends on interactions of cancer cells with the tumor microenvironment. Here, we find increased copy number and mRNA expression of the catalytic subunit of telomerase, TERT, in tumors from NSCLC patients, contributing to a lower survival. Moreover, TERT expression in NSCLC patients from the TCGA cohort is mainly associated to the reduced infiltration of CD8+ T lymphocytes, as well as to increased infiltration of myeloid-derived suppressor cells (MDSCs). We also show that TERT deficiency and dysfunctional telomeres induced by 6-thio-dG treatment in mice reduced lung tumor implantation and vascularization, increased DNA damage response, cell cycle arrest and apoptosis, as well as reduced proliferation, inflammation, lung tumor immunosupression and invasion upon induction of a Lewis lung carcinoma (LLC). Furthermore, 6-thio-dG-treated human NSCLC xenografts exhibited increased telomere damage, cell cycle arrest and apoptosis, as well as reduced proliferation, resulting in a reduced tumor growth. Our results show that targeting telomeres might be an effective therapeutic strategy in NSCLC.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023-06-01
2023
2023-06-01
2024
2024-03-18
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
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/20.500.12105/18977
url http://hdl.handle.net/20.500.12105/18977
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv European Commission http://dx.doi.org/10.13039/501100000780 Horizon 2020 Framework Programme 882385
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
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 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/vnd.openxmlformats-officedocument.wordprocessingml.document
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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