Hypoxic and Reoxygenated Microenvironment: Stemness and Differentiation State in Glioblastoma.

MARIANA MAIER GAELZER; ALICE HOFFMAN DE QUADROS; FÁTIMA COSTA RODRIGUES GUMA; CHRISTIANNE G. SALBGO; MARIANA SILVA DOS SANTOS; FABRÍCIO SIMÃO; BÁRBARA PARANHOS COELHO; SETTON - AVRUJ, PATRICIA; USACH, VANINA; GUIDO LENZ

MOLECULAR NEUROBIOLOGY

HUMANA PRESS INC

Lugar: Oregon; Año: 2016

0893-7648

Glioblastoma (GBM) is the most common and aggressiveprimary malignant brain tumor in adults. Hypoxia is adistinct feature in GBM and plays a significant role in tumorprogression, resistance to treatment, and poor outcome.However, there is lack of studies relating type of cell death,status of Akt phosphorylation on Ser473, mitochondrial membranepotential, and morphological changes of tumor cellsafter hypoxia and reoxygenation. The rat glioma C6 cell linewas exposed to oxygen deprivation (OD) in 5 % fetal bovineserum (FBS) or serum-free media followed by reoxygenation(RO). OD induced apoptosis on both 5% FBS and serum-freegroups. Overall, cells on serum-free media showed more profoundmorphological changes than cells on 5 % FBS.Moreover, our results suggest that OD combined with absenceof serum provided a favorable environment for glioblastomadedifferentiation to cancer stem cells, since nestin, and CD133levels increased. Reoxygenation is present in hypoxic tumorsthrough microvessel formation and cell migration to oxygenatedareas. However, few studies approach these phenomenawhen analyzing hypoxia. We show that RO caused morphologicalalterations characteristic of cells undergoing a differentiationprocess due to increased GFAP. In the present study,we characterized an in vitro hypoxic microenvironment associatedwith GBM tumors, therefore contributing with newinsights for the development of therapeutics for resistantglioblastoma.