Neutrophils drive endoplasmic reticulum stress-mediated apoptosis in cancer cells through arginase-1 release

Abstract Human neutrophils constitutively express high amounts of arginase-1, which depletes arginine from the surrounding medium and downregulates T-cell activation. Here, we have found that neutrophil arginase-1, released from activated human neutrophils or dead cells, induced apoptosis in cancer...

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Autores principales:	Rósula García-Navas, Consuelo Gajate, Faustino Mollinedo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b3ca417bc36d4ead837f65be523db8d4
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spelling	oai:doaj.org-article:b3ca417bc36d4ead837f65be523db8d42021-12-02T17:40:46ZNeutrophils drive endoplasmic reticulum stress-mediated apoptosis in cancer cells through arginase-1 release10.1038/s41598-021-91947-02045-2322https://doaj.org/article/b3ca417bc36d4ead837f65be523db8d42021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91947-0https://doaj.org/toc/2045-2322Abstract Human neutrophils constitutively express high amounts of arginase-1, which depletes arginine from the surrounding medium and downregulates T-cell activation. Here, we have found that neutrophil arginase-1, released from activated human neutrophils or dead cells, induced apoptosis in cancer cells through an endoplasmic reticulum (ER) stress pathway. Silencing of PERK in cancer cells prevented the induction of ER stress and apoptosis. Arginase inhibitor Nω-hydroxy-nor-arginine inhibited apoptosis and ER stress response induced by conditioned medium from activated neutrophils. A number of tumor cell lines, derived from different tissues, were sensitive to neutrophil arginase-1, with pancreatic, breast, ovarian and lung cancer cells showing the highest sensitivity. Neutrophil-released arginase-1 and arginine deprivation potentiated the antitumor action against pancreatic cancer cells of the ER-targeted antitumor alkylphospholipid analog edelfosine. Our study demonstrates the involvement of neutrophil arginase-1 in cancer cell killing and highlights the importance and complex role of neutrophils in tumor surveillance and biology.Rósula García-NavasConsuelo GajateFaustino MollinedoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rósula García-Navas Consuelo Gajate Faustino Mollinedo Neutrophils drive endoplasmic reticulum stress-mediated apoptosis in cancer cells through arginase-1 release
description	Abstract Human neutrophils constitutively express high amounts of arginase-1, which depletes arginine from the surrounding medium and downregulates T-cell activation. Here, we have found that neutrophil arginase-1, released from activated human neutrophils or dead cells, induced apoptosis in cancer cells through an endoplasmic reticulum (ER) stress pathway. Silencing of PERK in cancer cells prevented the induction of ER stress and apoptosis. Arginase inhibitor Nω-hydroxy-nor-arginine inhibited apoptosis and ER stress response induced by conditioned medium from activated neutrophils. A number of tumor cell lines, derived from different tissues, were sensitive to neutrophil arginase-1, with pancreatic, breast, ovarian and lung cancer cells showing the highest sensitivity. Neutrophil-released arginase-1 and arginine deprivation potentiated the antitumor action against pancreatic cancer cells of the ER-targeted antitumor alkylphospholipid analog edelfosine. Our study demonstrates the involvement of neutrophil arginase-1 in cancer cell killing and highlights the importance and complex role of neutrophils in tumor surveillance and biology.
format	article
author	Rósula García-Navas Consuelo Gajate Faustino Mollinedo
author_facet	Rósula García-Navas Consuelo Gajate Faustino Mollinedo
author_sort	Rósula García-Navas
title	Neutrophils drive endoplasmic reticulum stress-mediated apoptosis in cancer cells through arginase-1 release
title_short	Neutrophils drive endoplasmic reticulum stress-mediated apoptosis in cancer cells through arginase-1 release
title_full	Neutrophils drive endoplasmic reticulum stress-mediated apoptosis in cancer cells through arginase-1 release
title_fullStr	Neutrophils drive endoplasmic reticulum stress-mediated apoptosis in cancer cells through arginase-1 release
title_full_unstemmed	Neutrophils drive endoplasmic reticulum stress-mediated apoptosis in cancer cells through arginase-1 release
title_sort	neutrophils drive endoplasmic reticulum stress-mediated apoptosis in cancer cells through arginase-1 release
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/b3ca417bc36d4ead837f65be523db8d4
work_keys_str_mv	AT rosulagarcianavas neutrophilsdriveendoplasmicreticulumstressmediatedapoptosisincancercellsthrougharginase1release AT consuelogajate neutrophilsdriveendoplasmicreticulumstressmediatedapoptosisincancercellsthrougharginase1release AT faustinomollinedo neutrophilsdriveendoplasmicreticulumstressmediatedapoptosisincancercellsthrougharginase1release
_version_	1718379784326610944

Neutrophils drive endoplasmic reticulum stress-mediated apoptosis in cancer cells through arginase-1 release

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