MMP1 drives tumor progression in large cell carcinoma of the lung through fibroblast senescence

Large cell carcinoma (LCC) is a rare and aggressive lung cancer subtype with poor prognosis and no targeted therapies. Tumor-associated fibroblasts (TAFs) derived from LCC tumors exhibit premature senescence, and coculture of pulmonary fibroblasts with LCC cell lines selectively induces fibroblast s...

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Autores: Ikemori, Rafael, Llorente, A, Maqueda González, María de los Ángeles|||0000-0001-9304-1714, Dávalos Errando, Antoni, Perera Lluna, Alexandre|||0000-0001-6427-851X, Reguart, Noemí, Quiroz, Luis, Alcaraz Casademunt, Jordi
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universitat Politècnica de Catalunya (UPC)
Repositorio:UPCommons. Portal del coneixement obert de la UPC
Idioma:inglés
OAI Identifier:oai:upcommons.upc.edu:2117/345329
Acceso en línea:https://hdl.handle.net/2117/345329
https://dx.doi.org/10.1016/j.canlet.2021.01.028
Access Level:acceso abierto
Palabra clave:Lungs--Cancer
MMP1
Cancer-associated fibroblasts
SenescenceTGF-ß
Lung cancer
Pulmons -- Càncer
Àrees temàtiques de la UPC::Ciències de la salut
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spelling MMP1 drives tumor progression in large cell carcinoma of the lung through fibroblast senescenceIkemori, RafaelLlorente, AMaqueda González, María de los Ángeles|||0000-0001-9304-1714Dávalos Errando, AntoniPerera Lluna, Alexandre|||0000-0001-6427-851XReguart, NoemíQuiroz, LuisAlcaraz Casademunt, JordiLungs--CancerMMP1Cancer-associated fibroblastsSenescenceTGF-ßLung cancerPulmons -- CàncerÀrees temàtiques de la UPC::Ciències de la salutLarge cell carcinoma (LCC) is a rare and aggressive lung cancer subtype with poor prognosis and no targeted therapies. Tumor-associated fibroblasts (TAFs) derived from LCC tumors exhibit premature senescence, and coculture of pulmonary fibroblasts with LCC cell lines selectively induces fibroblast senescence, which in turn drives LCC cell growth and invasion. Here we identify MMP1 as overexpressed specifically in LCC cell lines, and we show that expression of MMP1 by LCC cells is necessary for induction of fibroblast senescence and consequent tumor promotion in both cell culture and mouse models. We also show that MMP1, in combination with TGF-ß1, is sufficient to induce fibroblast senescence and consequent LCC promotion. Furthermore, we implicate PAR-1 and oxidative stress in MMP1/TGF-ß1-induced TAF senescence. Our results establish an entirely new role for MMP1 in cancer, and support a novel therapeutic strategy in LCC based on targeting senescent TAFs.Peer Reviewed20212021-03-0120212021-05-10journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/2117/345329https://dx.doi.org/10.1016/j.canlet.2021.01.028reponame:UPCommons. Portal del coneixement obert de la UPCinstname:Universitat Politècnica de Catalunya (UPC)InglésengEuropean Commission http://doi.org/10.13039/100010661 Horizon 2020 Framework Programme 780262 Social media platform dedicated to rare diseases, using collective intelligence for the generation of awareness and advanced knowledge on this large group of diseases.Agencia Estatal de Investigación http://doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 DPI2017-89827-R RENDIMIENTO EN ALTURA EN ATLETAS DE ELITE: ANALISI DE FACTORES GENETICOS, METABOLICOS Y NERUOCARDIOVASCULARES EN ENTRENAMIENTO Y COMPETICION.open accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivs 3.0 Spainhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/info:eu-repo/semantics/openAccessoai:upcommons.upc.edu:2117/3453292026-05-27T15:37:01Z
dc.title.none.fl_str_mv MMP1 drives tumor progression in large cell carcinoma of the lung through fibroblast senescence
title MMP1 drives tumor progression in large cell carcinoma of the lung through fibroblast senescence
spellingShingle MMP1 drives tumor progression in large cell carcinoma of the lung through fibroblast senescence
Ikemori, Rafael
Lungs--Cancer
MMP1
Cancer-associated fibroblasts
SenescenceTGF-ß
Lung cancer
Pulmons -- Càncer
Àrees temàtiques de la UPC::Ciències de la salut
title_short MMP1 drives tumor progression in large cell carcinoma of the lung through fibroblast senescence
title_full MMP1 drives tumor progression in large cell carcinoma of the lung through fibroblast senescence
title_fullStr MMP1 drives tumor progression in large cell carcinoma of the lung through fibroblast senescence
title_full_unstemmed MMP1 drives tumor progression in large cell carcinoma of the lung through fibroblast senescence
title_sort MMP1 drives tumor progression in large cell carcinoma of the lung through fibroblast senescence
dc.creator.none.fl_str_mv Ikemori, Rafael
Llorente, A
Maqueda González, María de los Ángeles|||0000-0001-9304-1714
Dávalos Errando, Antoni
Perera Lluna, Alexandre|||0000-0001-6427-851X
Reguart, Noemí
Quiroz, Luis
Alcaraz Casademunt, Jordi
author Ikemori, Rafael
author_facet Ikemori, Rafael
Llorente, A
Maqueda González, María de los Ángeles|||0000-0001-9304-1714
Dávalos Errando, Antoni
Perera Lluna, Alexandre|||0000-0001-6427-851X
Reguart, Noemí
Quiroz, Luis
Alcaraz Casademunt, Jordi
author_role author
author2 Llorente, A
Maqueda González, María de los Ángeles|||0000-0001-9304-1714
Dávalos Errando, Antoni
Perera Lluna, Alexandre|||0000-0001-6427-851X
Reguart, Noemí
Quiroz, Luis
Alcaraz Casademunt, Jordi
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Lungs--Cancer
MMP1
Cancer-associated fibroblasts
SenescenceTGF-ß
Lung cancer
Pulmons -- Càncer
Àrees temàtiques de la UPC::Ciències de la salut
topic Lungs--Cancer
MMP1
Cancer-associated fibroblasts
SenescenceTGF-ß
Lung cancer
Pulmons -- Càncer
Àrees temàtiques de la UPC::Ciències de la salut
description Large cell carcinoma (LCC) is a rare and aggressive lung cancer subtype with poor prognosis and no targeted therapies. Tumor-associated fibroblasts (TAFs) derived from LCC tumors exhibit premature senescence, and coculture of pulmonary fibroblasts with LCC cell lines selectively induces fibroblast senescence, which in turn drives LCC cell growth and invasion. Here we identify MMP1 as overexpressed specifically in LCC cell lines, and we show that expression of MMP1 by LCC cells is necessary for induction of fibroblast senescence and consequent tumor promotion in both cell culture and mouse models. We also show that MMP1, in combination with TGF-ß1, is sufficient to induce fibroblast senescence and consequent LCC promotion. Furthermore, we implicate PAR-1 and oxidative stress in MMP1/TGF-ß1-induced TAF senescence. Our results establish an entirely new role for MMP1 in cancer, and support a novel therapeutic strategy in LCC based on targeting senescent TAFs.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021-03-01
2021
2021-05-10
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 https://hdl.handle.net/2117/345329
https://dx.doi.org/10.1016/j.canlet.2021.01.028
url https://hdl.handle.net/2117/345329
https://dx.doi.org/10.1016/j.canlet.2021.01.028
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv European Commission http://doi.org/10.13039/100010661 Horizon 2020 Framework Programme 780262 Social media platform dedicated to rare diseases, using collective intelligence for the generation of awareness and advanced knowledge on this large group of diseases.
Agencia Estatal de Investigación http://doi.org/10.13039/501100011033 Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 DPI2017-89827-R RENDIMIENTO EN ALTURA EN ATLETAS DE ELITE: ANALISI DE FACTORES GENETICOS, METABOLICOS Y NERUOCARDIOVASCULARES EN ENTRENAMIENTO Y COMPETICION.
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivs 3.0 Spain
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
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-NoDerivs 3.0 Spain
http://creativecommons.org/licenses/by-nc-nd/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:UPCommons. Portal del coneixement obert de la UPC
instname:Universitat Politècnica de Catalunya (UPC)
instname_str Universitat Politècnica de Catalunya (UPC)
reponame_str UPCommons. Portal del coneixement obert de la UPC
collection UPCommons. Portal del coneixement obert de la UPC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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