Stroma-derived IL-6, G-CSF and Activin-A mediated dedifferentiation of lung carcinoma cells into cancer stem cells
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/108042 https://doi.org/10.1038/s41598-018-29947-w |
Resumo: | 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. |
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Stroma-derived IL-6, G-CSF and Activin-A mediated dedifferentiation of lung carcinoma cells into cancer stem cellsActivinsAnimalsCarcinogenesisCell DifferentiationCell Line, TumorCoculture TechniquesGranulocyte Colony-Stimulating FactorHumansInterleukin-6Mice, Inbred BALB CMice, SCIDNeoplasms, ExperimentalNeoplastic Stem CellsStromal CellsCancer 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.Springer Nature2018-08-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/108042http://hdl.handle.net/10316/108042https://doi.org/10.1038/s41598-018-29947-weng2045-2322Rodrigues, Carlos F. D.Serrano, EuricoPatrício, Maria I.Val, MarianaAlbuquerque, PatríciaFonseca, JoãoGomes, Célia M. F.Abrunhosa, AnteroPaiva, ArturCarvalho, LinaBotelho, Maria F.Almeida, LuísCarreira, Isabel M.Alpoim, Maria Carmeninfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-08-07T11:40:25Zoai:estudogeral.uc.pt:10316/108042Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:24:18.861216Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Stroma-derived IL-6, G-CSF and Activin-A mediated dedifferentiation of lung carcinoma cells into cancer stem cells |
title |
Stroma-derived IL-6, G-CSF and Activin-A mediated dedifferentiation of lung carcinoma cells into cancer stem cells |
spellingShingle |
Stroma-derived IL-6, G-CSF and Activin-A mediated dedifferentiation of lung carcinoma cells into cancer stem cells Rodrigues, Carlos F. D. Activins Animals Carcinogenesis Cell Differentiation Cell Line, Tumor Coculture Techniques Granulocyte Colony-Stimulating Factor Humans Interleukin-6 Mice, Inbred BALB C Mice, SCID Neoplasms, Experimental Neoplastic Stem Cells Stromal 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 |
author |
Rodrigues, Carlos F. D. |
author_facet |
Rodrigues, Carlos F. D. Serrano, Eurico Patrício, Maria I. Val, Mariana Albuquerque, Patrícia Fonseca, João Gomes, Célia M. F. Abrunhosa, Antero Paiva, Artur Carvalho, Lina Botelho, Maria F. Almeida, Luís Carreira, Isabel M. Alpoim, Maria Carmen |
author_role |
author |
author2 |
Serrano, Eurico Patrício, Maria I. Val, Mariana Albuquerque, Patrícia Fonseca, João Gomes, Célia M. F. Abrunhosa, Antero Paiva, Artur Carvalho, Lina Botelho, Maria F. Almeida, Luís Carreira, Isabel M. Alpoim, Maria Carmen |
author2_role |
author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Rodrigues, Carlos F. D. Serrano, Eurico Patrício, Maria I. Val, Mariana Albuquerque, Patrícia Fonseca, João Gomes, Célia M. F. Abrunhosa, Antero Paiva, Artur Carvalho, Lina Botelho, Maria F. Almeida, Luís Carreira, Isabel M. Alpoim, Maria Carmen |
dc.subject.por.fl_str_mv |
Activins Animals Carcinogenesis Cell Differentiation Cell Line, Tumor Coculture Techniques Granulocyte Colony-Stimulating Factor Humans Interleukin-6 Mice, Inbred BALB C Mice, SCID Neoplasms, Experimental Neoplastic Stem Cells Stromal Cells |
topic |
Activins Animals Carcinogenesis Cell Differentiation Cell Line, Tumor Coculture Techniques Granulocyte Colony-Stimulating Factor Humans Interleukin-6 Mice, Inbred BALB C Mice, SCID Neoplasms, Experimental Neoplastic Stem Cells Stromal Cells |
description |
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. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-08-01 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/108042 http://hdl.handle.net/10316/108042 https://doi.org/10.1038/s41598-018-29947-w |
url |
http://hdl.handle.net/10316/108042 https://doi.org/10.1038/s41598-018-29947-w |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2045-2322 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Springer Nature |
publisher.none.fl_str_mv |
Springer Nature |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799134128470228992 |