Short-Term Differentiation of Glioblastoma Stem Cells Induces Hypoxia Tolerance.

Short-Term Differentiation of Glioblastoma Stem Cells Induces Hypoxia Tolerance.
Neurochem Res. 2016 Feb 25;
Authors: Skjellegrind HK, Fayzullin A, Johnsen EO, Eide L, Langmoen IA, Moe MC, Vik-Mo EO
Abstract
Glioblastoma is the most common and malignant brain cancer. In spite of surgical removal, radiation and chemotherapy, this cancer recurs within short time and median survival after diagnosis is less than a year. Glioblastoma stem cells (GSCs) left in the brain after surgery is thought to explain the inevitable recurrence of the tumor. Although hypoxia is a prime factor contributing to treatment resistance in many cancers, its effect on GSC has been little studied. Especially how differentiation influences the tolerance to acute hypoxia in GSCs is not well explored. We cultured GSCs from three patient biopsies and exposed these and their differentiated (1- and 4-weeks) progeny to acute hypoxia while monitoring intracellular calcium and mitochondrial membrane potential (ΔΨm). Undifferentiated GSCs were not hypoxia tolerant, showing both calcium overload and mitochondrial depolarization. One week differentiated cells were the most tolerant to hypoxia, preserving intracellular calcium stability and ΔΨm during 15 min of acute hypoxia. After 4 weeks of differentiation, mitochondrial mass was significantly reduced. In these cells calcium homeostasis was maintained during hypoxia, although the mitochondria were depolarized, suggest...

Source: Neurochemical Research - February 25, 2016 Category: Neuroscience Authors: Skjellegrind HK, Fayzullin A, Johnsen EO, Eide L, Langmoen IA, Moe MC, Vik-Mo EO Tags: Neurochem Res Source Type: research