Stroma-derived IL-6, G-CSF and Activin-A mediated dedifferentiation of lung carcinoma cells into cancer stem cells

Abstract Cancer stem cells (CSCs) are a small population of resistant cells inhabiting the tumors. Although comprising only nearly 3% of the tumor mass, these cells were demonstrated to orchestrate tumorigenesis and differentiation, underlie tumors’ heterogeneity and mediate therapy resistance and t...

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Autores principales:	Carlos F. D. Rodrigues, Eurico Serrano, Maria I. Patrício, Mariana M. Val, Patrícia Albuquerque, João Fonseca, Célia M. F. Gomes, Antero J. Abrunhosa, Artur Paiva, Lina Carvalho, M. Filomena Botelho, Luís Almeida, Isabel M. Carreira, Maria Carmen Alpoim
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6bb37cff1bbf4fc29ff5c570d306e16b
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spelling	oai:doaj.org-article:6bb37cff1bbf4fc29ff5c570d306e16b2021-12-02T11:41:14ZStroma-derived IL-6, G-CSF and Activin-A mediated dedifferentiation of lung carcinoma cells into cancer stem cells10.1038/s41598-018-29947-w2045-2322https://doaj.org/article/6bb37cff1bbf4fc29ff5c570d306e16b2018-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-29947-whttps://doaj.org/toc/2045-2322Abstract Cancer stem cells (CSCs) are a small population of resistant cells inhabiting the tumors. Although comprising only nearly 3% of the tumor mass, these cells were demonstrated to orchestrate tumorigenesis and differentiation, underlie tumors’ heterogeneity and mediate therapy resistance and tumor relapse. Here we show that CSCs may be formed by dedifferentiation of terminally differentiated tumor cells under stress conditions. Using a elegant co-culture cellular system, we were able to prove that nutrients and oxygen deprivation activated non-malignant stromal fibroblasts, which in turn established with tumor cells a paracrine loop mediated by Interleukine-6 (IL-6), Activin-A and Granulocyte colony-stimulating factor (G-CSF), that drove subsequent tumor formation and cellular dedifferentiation. However, by scavenging these cytokines from the media and/or blocking exosomes’ mediated communication it was possible to abrogate dedifferentiation thus turning these mechanisms into potential therapeutic targets against cancer progression.Carlos F. D. RodriguesEurico SerranoMaria I. PatrícioMariana M. ValPatrícia AlbuquerqueJoão FonsecaCélia M. F. GomesAntero J. AbrunhosaArtur PaivaLina CarvalhoM. Filomena BotelhoLuís AlmeidaIsabel M. CarreiraMaria Carmen AlpoimNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-12 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Carlos F. D. Rodrigues Eurico Serrano Maria I. Patrício Mariana M. Val Patrícia Albuquerque João Fonseca Célia M. F. Gomes Antero J. Abrunhosa Artur Paiva Lina Carvalho M. Filomena Botelho Luís Almeida Isabel M. Carreira Maria Carmen Alpoim Stroma-derived IL-6, G-CSF and Activin-A mediated dedifferentiation of lung carcinoma cells into cancer stem cells
description	Abstract Cancer stem cells (CSCs) are a small population of resistant cells inhabiting the tumors. Although comprising only nearly 3% of the tumor mass, these cells were demonstrated to orchestrate tumorigenesis and differentiation, underlie tumors’ heterogeneity and mediate therapy resistance and tumor relapse. Here we show that CSCs may be formed by dedifferentiation of terminally differentiated tumor cells under stress conditions. Using a elegant co-culture cellular system, we were able to prove that nutrients and oxygen deprivation activated non-malignant stromal fibroblasts, which in turn established with tumor cells a paracrine loop mediated by Interleukine-6 (IL-6), Activin-A and Granulocyte colony-stimulating factor (G-CSF), that drove subsequent tumor formation and cellular dedifferentiation. However, by scavenging these cytokines from the media and/or blocking exosomes’ mediated communication it was possible to abrogate dedifferentiation thus turning these mechanisms into potential therapeutic targets against cancer progression.
format	article
author	Carlos F. D. Rodrigues Eurico Serrano Maria I. Patrício Mariana M. Val Patrícia Albuquerque João Fonseca Célia M. F. Gomes Antero J. Abrunhosa Artur Paiva Lina Carvalho M. Filomena Botelho Luís Almeida Isabel M. Carreira Maria Carmen Alpoim
author_facet	Carlos F. D. Rodrigues Eurico Serrano Maria I. Patrício Mariana M. Val Patrícia Albuquerque João Fonseca Célia M. F. Gomes Antero J. Abrunhosa Artur Paiva Lina Carvalho M. Filomena Botelho Luís Almeida Isabel M. Carreira Maria Carmen Alpoim
author_sort	Carlos F. D. Rodrigues
title	Stroma-derived IL-6, G-CSF and Activin-A mediated dedifferentiation of lung carcinoma cells into cancer stem cells
title_short	Stroma-derived IL-6, G-CSF and Activin-A mediated dedifferentiation of lung carcinoma cells into cancer stem cells
title_full	Stroma-derived IL-6, G-CSF and Activin-A mediated dedifferentiation of lung carcinoma cells into cancer stem cells
title_fullStr	Stroma-derived IL-6, G-CSF and Activin-A mediated dedifferentiation of lung carcinoma cells into cancer stem cells
title_full_unstemmed	Stroma-derived IL-6, G-CSF and Activin-A mediated dedifferentiation of lung carcinoma cells into cancer stem cells
title_sort	stroma-derived il-6, g-csf and activin-a mediated dedifferentiation of lung carcinoma cells into cancer stem cells
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/6bb37cff1bbf4fc29ff5c570d306e16b
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Stroma-derived IL-6, G-CSF and Activin-A mediated dedifferentiation of lung carcinoma cells into cancer stem cells

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