Artículo
Hypoxic and reoxygenated microenvironment: stemness and differentiation state in glioblastoma
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.
Fecha de publicación:
10/2016
Editorial:
Springer
Revista:
Molecular Neurobiology
ISSN:
0893-7648
e-ISSN:
1559-1182
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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.
Palabras clave:
Cancer
,
Glioma
,
Hypoxia
,
Reoxygenation
,
C6
,
Cancer Stem Cell
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Colecciones
Articulos(IQUIFIB)
Articulos de INST.DE QUIMICA Y FISICO-QUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Articulos de INST.DE QUIMICA Y FISICO-QUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Citación
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
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