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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/21315
Ver los metadatos del registro completo
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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 Técnicas2025-09-29T09:52:02Zoai: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:34982025-09-29 09:52:03.096CONICET 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 |
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CONICET Digital (CONICET) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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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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13.070432 |