Abstract 5205: Iron metabolism informs glioblastoma stem cell maintenance

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Glioblastoma is a highly lethal cancer that is characterized by florid angiogenesis, invasion into normal brain, and therapeutic resistance. Glioblastomas display cellular hierarchies with a self-renewing, tumorigenic glioblastoma stem cell (GSC) at the apex. The significance of GSCs in tumor biology has been supported by work from our group and others showing that GSCs are relatively resistant to conventional therapies, promote tumor angiogenesis, and are highly invasive. By comparing GSCs to matched differentiated tumor bulk, we have identified a number of molecular targets that function in maintenance of the cellular hierarchy and tumor growth. We have now identified increased iron metabolism as a characteristic of GSCs. Normal glial progenitors accumulate iron to increase migration and proliferation. Brain tumors accumulate iron and iron regulators are associated with poor survival. As hypoxia induces iron regulators and maintains the cellular hierarchy, we are investigating iron regulation in GSCs. Ectopic delivery of iron to GSCs increases tumorsphere growth while disrupting iron metabolism in GSCs using shRNA reduces cell growth and decreases the expression of angiogenic growth factors. Collectively, these results suggest that iron metabolism is important for GSC maintenance and tumorigenic potential. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5205. doi:1538-7445.AM2012-5205