title: Hypoxic and Reoxygenated Microenvironment: Stemness and Differentiation State in Glioblastoma.
abstract: 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.
authors.affiliation: Biochemistry Department, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil. marianamaierg@gmail.com.|Biochemistry Department, Institute of Health Sciences, 2600 Ramiro Barcelos Street, Porto Alegre, RS, 90035-003, Brazil. marianamaierg@gmail.com.
authors.forename: Mariana Maier
authors.initials: MM
authors.lastname: Gaelzer
authors.affiliation: Biochemistry Department, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Mariana Silva Dos
authors.initials: MSD
authors.lastname: Santos
authors.affiliation: Biochemistry Department, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Bárbara Paranhos
authors.initials: BP
authors.lastname: Coelho
authors.affiliation: Biochemistry Department, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Alice Hoffman
authors.initials: AH
authors.lastname: de Quadros
authors.affiliation: Harvard Medical School Joslin Diabetes Center, Boston, MA, USA.
authors.forename: Fabrício
authors.initials: F
authors.lastname: Simão
authors.affiliation: Biological Chemistry Department, University of Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Vanina
authors.initials: V
authors.lastname: Usach
authors.affiliation: Biochemistry Department, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Fátima Costa Rodrigues
authors.initials: FCR
authors.lastname: Guma
authors.affiliation: Biological Chemistry Department, University of Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Setton-Avruj
authors.affiliation: Biophysics Department, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Guido
authors.initials: G
authors.lastname: Lenz
authors.affiliation: Biochemistry Department, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Christianne G
authors.initials: CG
authors.lastname: Salbego
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology*; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D010100:Oxygen / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D059016:Tumor Microenvironment
chemical_list: D051057:Proto-Oncogene Proteins c-akt; D010100:Oxygen
keywords: C6; Cancer; Cancer stem cell; Glioma; Hypoxia; Reoxygenation