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2014 Abstracts

Glioma stem cells, hypoxia inducible factor 1 alpha, and brain tumor dynamics

Bradley Weaver, University of Utah


High-grade gliomas, especially glioblastoma (GBMs, WHO Grade IV), are the most common primary brain tumors in humans. Despite recent advances in molecular targeted therapies for cancer, there has been little progress in treatment of GBMs. Median patient survival after diagnosis is dismal: approximately 12 months. Hypoxia is a key clinical marker of GBMs, which contain pockets of necrotic and hypoxic regions within the solid tumor mass. The transcription factors in the Hypoxia Inducible Factor (HIF) family are the master regulators of the cellular response to hypoxia. Their downstream targets include compounds that promote angiogenesis, increase glycolysis, and inhibit apoptosis. Recent research has identified glioma stem cells (GSCs) surviving within the hypoxic microenvironment, and has implicated HIF1α as a potential regulator of the GSC phenotype. GSCs are thought to promote therapeutic resistance and recurrence of GBMs after surgical resection. Clarifying the role of HIF1α in glioma stem cell dynamics is important for targeting both the tumor cells and their environment in new treatment. It is expected that GSC populations with more aggressive phenotypes will express higher levels of HIF1α and have higher proliferation rates under acute hypoxia. In this study, the HIF1α levels and proliferation dynamics of multiple, unique GSC cell lines are investigated. Cell lines used include two GSC lines isolated from primary patient tumors (NSC20/23) and a stem cell enriched high-grade glioma line. Preliminary results suggest that not all populations of GSCs respond the same way to hypoxic stress, and HIF1α may play a central role in stem cell dynamics, but not in the growth of non-stem tumor cells. Probing further into this relationship will increase our understanding of how brain tumors behave, and how to more effectively target them in patients. Further data and conclusions from this project will be available at the time of presentation.