Hypoxic and reoxygenated microenvironment: stemness and differentiation state in glioblastoma

Autores
Maier Gaelzer, Mariana; Silva dos Santos, Mariana; Paranhos Coelho, Bárbara; de Quadros, Alice Hoffman; Simão, Fabrício; Usach, Vanina; Guma, Fátima Costa Rodrigues; Setton, Clara Patricia; Lenz, Guido; Salbego, Christianne G.
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor in adults. Hypoxia is a distinct feature in GBM and plays a significant role in tumor progression, resistance to treatment, and poor outcome. However, there is lack of studies relating type of cell death, status of Akt phosphorylation on Ser473, mitochondrial membrane potential, and morphological changes of tumor cells after hypoxia and reoxygenation. The rat glioma C6 cell line was exposed to oxygen deprivation (OD) in 5 % fetal bovine serum (FBS) or serum-free media followed by reoxygenation (RO). OD induced apoptosis on both 5 % FBS and serum-free groups. Overall, cells on serum-free media showed more profound morphological changes than cells on 5 % FBS. Moreover, our results suggest that OD combined with absence of serum provided a favorable environment for glioblastoma dedifferentiation to cancer stem cells, since nestin, and CD133 levels increased. Reoxygenation is present in hypoxic tumors through microvessel formation and cell migration to oxygenated areas. However, few studies approach these phenomena when analyzing hypoxia. We show that RO caused morphological alterations characteristic of cells undergoing a differentiation process due to increased GFAP. In the present study, we characterized an in vitro hypoxic microenvironment associated with GBM tumors, therefore contributing with new insights for the development of therapeutics for resistant glioblastoma.
Fil: Maier Gaelzer, Mariana. Universidade Federal Do Rio Grande Do Sul. Instituto de Ciências Básicas da Saúde. Departamento de Bioquímica; Brasil
Fil: Silva dos Santos, Mariana. Universidade Federal Do Rio Grande Do Sul. Instituto de Ciências Básicas da Saúde. Departamento de Bioquímica; Brasil
Fil: Paranhos Coelho, Bárbara. Universidade Federal Do Rio Grande Do Sul. Instituto de Ciências Básicas da Saúde. Departamento de Bioquímica; Brasil
Fil: de Quadros, Alice Hoffman. Universidade Federal Do Rio Grande Do Sul. Instituto de Ciências Básicas da Saúde. Departamento de Bioquímica; Brasil
Fil: Simão, Fabrício. Harvard Medical School; Estados Unidos
Fil: Usach, Vanina. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Guma, Fátima Costa Rodrigues. Universidade Federal Do Rio Grande Do Sul. Instituto de Cs.basicas Da Saude. Dept.de Bioquímica; Brasil
Fil: Setton, Clara Patricia. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Lenz, Guido. Universidade Federal do Rio Grande do Sul; Brasil
Fil: Salbego, Christianne G.. Universidade Federal Do Rio Grande Do Sul. Instituto de Ciências Básicas da Saúde. Departamento de Bioquímica; Brasil
Materia
Cancer
Glioma
Hypoxia
Reoxygenation
C6
Cancer Stem Cell
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/21315
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/21315
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Hypoxic and reoxygenated microenvironment: stemness and differentiation state in glioblastomaMaier Gaelzer, MarianaSilva dos Santos, MarianaParanhos Coelho, Bárbarade Quadros, Alice HoffmanSimão, FabrícioUsach, VaninaGuma, Fátima Costa RodriguesSetton, Clara PatriciaLenz, GuidoSalbego, Christianne G.CancerGliomaHypoxiaReoxygenationC6Cancer Stem Cellhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor in adults. Hypoxia is a distinct feature in GBM and plays a significant role in tumor progression, resistance to treatment, and poor outcome. However, there is lack of studies relating type of cell death, status of Akt phosphorylation on Ser473, mitochondrial membrane potential, and morphological changes of tumor cells after hypoxia and reoxygenation. The rat glioma C6 cell line was exposed to oxygen deprivation (OD) in 5 % fetal bovine serum (FBS) or serum-free media followed by reoxygenation (RO). OD induced apoptosis on both 5 % FBS and serum-free groups. Overall, cells on serum-free media showed more profound morphological changes than cells on 5 % FBS. Moreover, our results suggest that OD combined with absence of serum provided a favorable environment for glioblastoma dedifferentiation to cancer stem cells, since nestin, and CD133 levels increased. Reoxygenation is present in hypoxic tumors through microvessel formation and cell migration to oxygenated areas. However, few studies approach these phenomena when analyzing hypoxia. We show that RO caused morphological alterations characteristic of cells undergoing a differentiation process due to increased GFAP. In the present study, we characterized an in vitro hypoxic microenvironment associated with GBM tumors, therefore contributing with new insights for the development of therapeutics for resistant glioblastoma.Fil: Maier Gaelzer, Mariana. Universidade Federal Do Rio Grande Do Sul. Instituto de Ciências Básicas da Saúde. Departamento de Bioquímica; BrasilFil: Silva dos Santos, Mariana. Universidade Federal Do Rio Grande Do Sul. Instituto de Ciências Básicas da Saúde. Departamento de Bioquímica; BrasilFil: Paranhos Coelho, Bárbara. Universidade Federal Do Rio Grande Do Sul. Instituto de Ciências Básicas da Saúde. Departamento de Bioquímica; BrasilFil: de Quadros, Alice Hoffman. Universidade Federal Do Rio Grande Do Sul. Instituto de Ciências Básicas da Saúde. Departamento de Bioquímica; BrasilFil: Simão, Fabrício. Harvard Medical School; Estados UnidosFil: Usach, Vanina. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Guma, Fátima Costa Rodrigues. Universidade Federal Do Rio Grande Do Sul. Instituto de Cs.basicas Da Saude. Dept.de Bioquímica; BrasilFil: Setton, Clara Patricia. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lenz, Guido. Universidade Federal do Rio Grande do Sul; BrasilFil: Salbego, Christianne G.. Universidade Federal Do Rio Grande Do Sul. Instituto de Ciências Básicas da Saúde. Departamento de Bioquímica; BrasilSpringer2016-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/21315Maier Gaelzer, Mariana; Silva dos Santos, Mariana; Paranhos Coelho, Bárbara; de Quadros, Alice Hoffman; Simão, Fabrício; et al.; Hypoxic and reoxygenated microenvironment: stemness and differentiation state in glioblastoma; Springer; Molecular Neurobiology; 53; 8; 10-2016; 1-120893-76481559-1182CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1007/s12035-016-0126-6info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs12035-016-0126-6info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:21:26Zoai:ri.conicet.gov.ar:11336/21315instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 11:21:27.192CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Hypoxic and reoxygenated microenvironment: stemness and differentiation state in glioblastoma
title Hypoxic and reoxygenated microenvironment: stemness and differentiation state in glioblastoma
spellingShingle Hypoxic and reoxygenated microenvironment: stemness and differentiation state in glioblastoma
Maier Gaelzer, Mariana
Cancer
Glioma
Hypoxia
Reoxygenation
C6
Cancer Stem Cell
title_short Hypoxic and reoxygenated microenvironment: stemness and differentiation state in glioblastoma
title_full Hypoxic and reoxygenated microenvironment: stemness and differentiation state in glioblastoma
title_fullStr Hypoxic and reoxygenated microenvironment: stemness and differentiation state in glioblastoma
title_full_unstemmed Hypoxic and reoxygenated microenvironment: stemness and differentiation state in glioblastoma
title_sort Hypoxic and reoxygenated microenvironment: stemness and differentiation state in glioblastoma
dc.creator.none.fl_str_mv Maier Gaelzer, Mariana
Silva dos Santos, Mariana
Paranhos Coelho, Bárbara
de Quadros, Alice Hoffman
Simão, Fabrício
Usach, Vanina
Guma, Fátima Costa Rodrigues
Setton, Clara Patricia
Lenz, Guido
Salbego, Christianne G.
author Maier Gaelzer, Mariana
author_facet Maier Gaelzer, Mariana
Silva dos Santos, Mariana
Paranhos Coelho, Bárbara
de Quadros, Alice Hoffman
Simão, Fabrício
Usach, Vanina
Guma, Fátima Costa Rodrigues
Setton, Clara Patricia
Lenz, Guido
Salbego, Christianne G.
author_role author
author2 Silva dos Santos, Mariana
Paranhos Coelho, Bárbara
de Quadros, Alice Hoffman
Simão, Fabrício
Usach, Vanina
Guma, Fátima Costa Rodrigues
Setton, Clara Patricia
Lenz, Guido
Salbego, Christianne G.
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cancer
Glioma
Hypoxia
Reoxygenation
C6
Cancer Stem Cell
topic Cancer
Glioma
Hypoxia
Reoxygenation
C6
Cancer Stem Cell
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor in adults. Hypoxia is a distinct feature in GBM and plays a significant role in tumor progression, resistance to treatment, and poor outcome. However, there is lack of studies relating type of cell death, status of Akt phosphorylation on Ser473, mitochondrial membrane potential, and morphological changes of tumor cells after hypoxia and reoxygenation. The rat glioma C6 cell line was exposed to oxygen deprivation (OD) in 5 % fetal bovine serum (FBS) or serum-free media followed by reoxygenation (RO). OD induced apoptosis on both 5 % FBS and serum-free groups. Overall, cells on serum-free media showed more profound morphological changes than cells on 5 % FBS. Moreover, our results suggest that OD combined with absence of serum provided a favorable environment for glioblastoma dedifferentiation to cancer stem cells, since nestin, and CD133 levels increased. Reoxygenation is present in hypoxic tumors through microvessel formation and cell migration to oxygenated areas. However, few studies approach these phenomena when analyzing hypoxia. We show that RO caused morphological alterations characteristic of cells undergoing a differentiation process due to increased GFAP. In the present study, we characterized an in vitro hypoxic microenvironment associated with GBM tumors, therefore contributing with new insights for the development of therapeutics for resistant glioblastoma.
Fil: Maier Gaelzer, Mariana. Universidade Federal Do Rio Grande Do Sul. Instituto de Ciências Básicas da Saúde. Departamento de Bioquímica; Brasil
Fil: Silva dos Santos, Mariana. Universidade Federal Do Rio Grande Do Sul. Instituto de Ciências Básicas da Saúde. Departamento de Bioquímica; Brasil
Fil: Paranhos Coelho, Bárbara. Universidade Federal Do Rio Grande Do Sul. Instituto de Ciências Básicas da Saúde. Departamento de Bioquímica; Brasil
Fil: de Quadros, Alice Hoffman. Universidade Federal Do Rio Grande Do Sul. Instituto de Ciências Básicas da Saúde. Departamento de Bioquímica; Brasil
Fil: Simão, Fabrício. Harvard Medical School; Estados Unidos
Fil: Usach, Vanina. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Guma, Fátima Costa Rodrigues. Universidade Federal Do Rio Grande Do Sul. Instituto de Cs.basicas Da Saude. Dept.de Bioquímica; Brasil
Fil: Setton, Clara Patricia. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Lenz, Guido. Universidade Federal do Rio Grande do Sul; Brasil
Fil: Salbego, Christianne G.. Universidade Federal Do Rio Grande Do Sul. Instituto de Ciências Básicas da Saúde. Departamento de Bioquímica; Brasil
description Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor in adults. Hypoxia is a distinct feature in GBM and plays a significant role in tumor progression, resistance to treatment, and poor outcome. However, there is lack of studies relating type of cell death, status of Akt phosphorylation on Ser473, mitochondrial membrane potential, and morphological changes of tumor cells after hypoxia and reoxygenation. The rat glioma C6 cell line was exposed to oxygen deprivation (OD) in 5 % fetal bovine serum (FBS) or serum-free media followed by reoxygenation (RO). OD induced apoptosis on both 5 % FBS and serum-free groups. Overall, cells on serum-free media showed more profound morphological changes than cells on 5 % FBS. Moreover, our results suggest that OD combined with absence of serum provided a favorable environment for glioblastoma dedifferentiation to cancer stem cells, since nestin, and CD133 levels increased. Reoxygenation is present in hypoxic tumors through microvessel formation and cell migration to oxygenated areas. However, few studies approach these phenomena when analyzing hypoxia. We show that RO caused morphological alterations characteristic of cells undergoing a differentiation process due to increased GFAP. In the present study, we characterized an in vitro hypoxic microenvironment associated with GBM tumors, therefore contributing with new insights for the development of therapeutics for resistant glioblastoma.
publishDate 2016
dc.date.none.fl_str_mv 2016-10
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/21315
Maier Gaelzer, Mariana; Silva dos Santos, Mariana; Paranhos Coelho, Bárbara; de Quadros, Alice Hoffman; Simão, Fabrício; et al.; Hypoxic and reoxygenated microenvironment: stemness and differentiation state in glioblastoma; Springer; Molecular Neurobiology; 53; 8; 10-2016; 1-12
0893-7648
1559-1182
CONICET Digital
CONICET
url http://hdl.handle.net/11336/21315
identifier_str_mv Maier Gaelzer, Mariana; Silva dos Santos, Mariana; Paranhos Coelho, Bárbara; de Quadros, Alice Hoffman; Simão, Fabrício; et al.; Hypoxic and reoxygenated microenvironment: stemness and differentiation state in glioblastoma; Springer; Molecular Neurobiology; 53; 8; 10-2016; 1-12
0893-7648
1559-1182
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1007/s12035-016-0126-6
info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs12035-016-0126-6
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.982451

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