Aldh1 Expression and Activity Increase During Tumor Evolution in Sarcoma Cancer Stem Cell Populations

Tumors evolve from initial tumorigenic events into increasingly aggressive behaviors in a process usually driven by subpopulations of cancer stem cells (CSCs). Mesenchymal stromal/stem cells (MSCs) may act as the cell-of-origin for sarcomas, and CSCs that present MSC features have been identified in...

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Detalles Bibliográficos
Autores: Martinez-Cruzado, Lucia, Tornin, Juan, Santos, Laura, Rodríguez, Aida, Garcia-Castro, Javier, Moris, Francisco, Rodriguez, Rene
Tipo de recurso: artículo
Fecha de publicación:2016
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/9158
Acceso en línea:http://hdl.handle.net/20.500.12105/9158
Access Level:acceso abierto
Palabra clave:Aldehyde Dehydrogenase 1
Animals
Cell Line, Tumor
Humans
Isoenzymes
Lung Neoplasms
Mice
Mice, Inbred NOD
Mice, SCID
Neoplastic Stem Cells
RNA Interference
RNA, Small Interfering
Retinal Dehydrogenase
SOXB1 Transcription Factors
Sarcoma
Time-Lapse Imaging
Transplantation, Heterologous
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repository_id_str
spelling Aldh1 Expression and Activity Increase During Tumor Evolution in Sarcoma Cancer Stem Cell PopulationsMartinez-Cruzado, LuciaTornin, JuanSantos, LauraRodríguez, AidaGarcia-Castro, JavierMoris, FranciscoRodriguez, ReneAldehyde Dehydrogenase 1AnimalsCell Line, TumorHumansIsoenzymesLung NeoplasmsMiceMice, Inbred NODMice, SCIDNeoplastic Stem CellsRNA InterferenceRNA, Small InterferingRetinal DehydrogenaseSOXB1 Transcription FactorsSarcomaTime-Lapse ImagingTransplantation, HeterologousTumors evolve from initial tumorigenic events into increasingly aggressive behaviors in a process usually driven by subpopulations of cancer stem cells (CSCs). Mesenchymal stromal/stem cells (MSCs) may act as the cell-of-origin for sarcomas, and CSCs that present MSC features have been identified in sarcomas due to their ability to grow as self-renewed floating spheres (tumorspheres). Accordingly, we previously developed sarcoma models using human MSCs transformed with relevant oncogenic events. To study the evolution/emergence of CSC subpopulations during tumor progression, we compared the tumorigenic properties of bulk adherent cultures and tumorsphere-forming subpopulations both in the sarcoma cell-of-origin models (transformed MSCs) and in their corresponding tumor xenograft-derived cells. Tumor formation assays showed that the tumorsphere cultures from xenograft-derived cells, but not from the cell-of-origin models, were enriched in CSCs, providing evidence of the emergence of bona fide CSCs subpopulations during tumor progression. Relevant CSC-related factors, such as ALDH1 and SOX2, were increasingly upregulated in CSCs during tumor progression, and importantly, the increased levels and activity of ALDH1 in these subpopulations were associated with enhanced tumorigenicity. In addition to being a CSC marker, our findings indicate that ALDH1 could also be useful for tracking the malignant potential of CSC subpopulations during sarcoma evolution.Nature Publishing GroupInstituto de Salud Carlos IIIMinisterio de Economía y Competitividad (España)Gobierno del Principado de Asturias (España)20202020-02-2820162016-01-0120162016-01-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/9158reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)InglésengES CP11 00024ES RD12 0036ES SAF-2013-42946-R Not availableES GRUPIN14-003 Not availableES RD12 0036open accesshttp://purl.org/coar/access_right/c_abf2Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/91582026-06-12T12:43:37Z
dc.title.none.fl_str_mv Aldh1 Expression and Activity Increase During Tumor Evolution in Sarcoma Cancer Stem Cell Populations
title Aldh1 Expression and Activity Increase During Tumor Evolution in Sarcoma Cancer Stem Cell Populations
spellingShingle Aldh1 Expression and Activity Increase During Tumor Evolution in Sarcoma Cancer Stem Cell Populations
Martinez-Cruzado, Lucia
Aldehyde Dehydrogenase 1
Animals
Cell Line, Tumor
Humans
Isoenzymes
Lung Neoplasms
Mice
Mice, Inbred NOD
Mice, SCID
Neoplastic Stem Cells
RNA Interference
RNA, Small Interfering
Retinal Dehydrogenase
SOXB1 Transcription Factors
Sarcoma
Time-Lapse Imaging
Transplantation, Heterologous
title_short Aldh1 Expression and Activity Increase During Tumor Evolution in Sarcoma Cancer Stem Cell Populations
title_full Aldh1 Expression and Activity Increase During Tumor Evolution in Sarcoma Cancer Stem Cell Populations
title_fullStr Aldh1 Expression and Activity Increase During Tumor Evolution in Sarcoma Cancer Stem Cell Populations
title_full_unstemmed Aldh1 Expression and Activity Increase During Tumor Evolution in Sarcoma Cancer Stem Cell Populations
title_sort Aldh1 Expression and Activity Increase During Tumor Evolution in Sarcoma Cancer Stem Cell Populations
dc.creator.none.fl_str_mv Martinez-Cruzado, Lucia
Tornin, Juan
Santos, Laura
Rodríguez, Aida
Garcia-Castro, Javier
Moris, Francisco
Rodriguez, Rene
author Martinez-Cruzado, Lucia
author_facet Martinez-Cruzado, Lucia
Tornin, Juan
Santos, Laura
Rodríguez, Aida
Garcia-Castro, Javier
Moris, Francisco
Rodriguez, Rene
author_role author
author2 Tornin, Juan
Santos, Laura
Rodríguez, Aida
Garcia-Castro, Javier
Moris, Francisco
Rodriguez, Rene
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Salud Carlos III
Ministerio de Economía y Competitividad (España)
Gobierno del Principado de Asturias (España)
dc.subject.none.fl_str_mv Aldehyde Dehydrogenase 1
Animals
Cell Line, Tumor
Humans
Isoenzymes
Lung Neoplasms
Mice
Mice, Inbred NOD
Mice, SCID
Neoplastic Stem Cells
RNA Interference
RNA, Small Interfering
Retinal Dehydrogenase
SOXB1 Transcription Factors
Sarcoma
Time-Lapse Imaging
Transplantation, Heterologous
topic Aldehyde Dehydrogenase 1
Animals
Cell Line, Tumor
Humans
Isoenzymes
Lung Neoplasms
Mice
Mice, Inbred NOD
Mice, SCID
Neoplastic Stem Cells
RNA Interference
RNA, Small Interfering
Retinal Dehydrogenase
SOXB1 Transcription Factors
Sarcoma
Time-Lapse Imaging
Transplantation, Heterologous
description Tumors evolve from initial tumorigenic events into increasingly aggressive behaviors in a process usually driven by subpopulations of cancer stem cells (CSCs). Mesenchymal stromal/stem cells (MSCs) may act as the cell-of-origin for sarcomas, and CSCs that present MSC features have been identified in sarcomas due to their ability to grow as self-renewed floating spheres (tumorspheres). Accordingly, we previously developed sarcoma models using human MSCs transformed with relevant oncogenic events. To study the evolution/emergence of CSC subpopulations during tumor progression, we compared the tumorigenic properties of bulk adherent cultures and tumorsphere-forming subpopulations both in the sarcoma cell-of-origin models (transformed MSCs) and in their corresponding tumor xenograft-derived cells. Tumor formation assays showed that the tumorsphere cultures from xenograft-derived cells, but not from the cell-of-origin models, were enriched in CSCs, providing evidence of the emergence of bona fide CSCs subpopulations during tumor progression. Relevant CSC-related factors, such as ALDH1 and SOX2, were increasingly upregulated in CSCs during tumor progression, and importantly, the increased levels and activity of ALDH1 in these subpopulations were associated with enhanced tumorigenicity. In addition to being a CSC marker, our findings indicate that ALDH1 could also be useful for tracking the malignant potential of CSC subpopulations during sarcoma evolution.
publishDate 2016
dc.date.none.fl_str_mv 2016
2016-01-01
2016
2016-01-01
2020
2020-02-28
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
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/20.500.12105/9158
url http://hdl.handle.net/20.500.12105/9158
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv ES CP11 00024
ES RD12 0036
ES SAF-2013-42946-R Not available
ES GRUPIN14-003 Not available
ES RD12 0036
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/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
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 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 15.812429

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