Knock down of HIF-1α in glioma cells reduces migration <it>in vitro </it>and invasion <it>in vivo </it>and impairs their ability to form tumor spheres

• Main Authors: Esencay Mine, Zavadil Jiri, Méndez Olga, Lukyanov Yevgeniy, Santovasi Daniel, Wang Shu-Chi, Newcomb Elizabeth W, Zagzag David
• Format: Article
• Language: English
• Published: BMC 2010-06-01
• Series: Molecular Cancer
• Online Access: http://www.molecular-cancer.com/content/9/1/133

<p>Abstract</p> <p>Background</p> <p>Glioblastoma (GBM) is the most common and malignant primary intracranial human neoplasm. GBMs are characterized by the presence of extensive areas of necrosis and hypoxia. Hypoxia and its master regulator, hypoxia inducible factor 1 (HIF-1) play a key role in glioma invasion.</p> <p>Results</p> <p>To further elucidate the functional role of HIF-1α in glioma cell migration <it>in vitro </it>and in invasion <it>in vivo</it>, we used a shRNA approach to knock down HIF-1α expression complemented with genome-wide expression profiling, performed in both normoxic and hypoxic conditions. Our data show that knock down of HIF-1α in glioma cells significantly impairs their migration <it>in vitro </it>as well as their ability to invade into the brain parenchyma <it>in vivo</it>. Next, we assessed the role that HIF-1α plays in maintaining the characteristics of cancer stem cells (CSCs). By using the tumor sphere forming assay, we demonstrate that HIF-1α plays a role in the survival and self-renewal potential of CSCs. Finally, expression profiling experiments in glioma cells provided detailed insight into a broad range of specific biological pathways and processes downstream of HIF-1α. We discuss the role of these processes in the migratory and invasive properties, as well as the stem cell biology of glioblastomas</p> <p>Conclusions</p> <p>Our data show that knock down of HIF-1α in human and murine glioma cells impairs their migration <it>in vitro </it>and their invasion <it>in vivo</it>. In addition, our data suggest that HIF-1α plays a role in the survival and self-renewal potential of CSCs and identify genes that might further elucidate the role of HIF-1α in tumor migration, invasion and stem cell biology.</p>