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

Molecular Cancer

Research

Yevgeniy Lukyanov¹  Daniel Santovasi¹  Shu-Chi Wang¹  Elizabeth W Newcomb²  Jiri Zavadil³  David Zagzag⁴  Mine Esencay⁵  Olga Méndez⁵ 

[1] Department of Pathology, New York University Langone Medical Center, New York, NY, USA;Department of Pathology, New York University Langone Medical Center, New York, NY, USA;New York University Cancer Institute, New York, NY, USA;Department of Pathology, New York University Langone Medical Center, New York, NY, USA;New York University Cancer Institute, New York, NY, USA;New York University Center for Health Informatics and Bioinformatics, New York University Langone Medical Center, New York, NY, USA;Microvascular and Molecular Neuro-oncology laboratory, New York University School of Medicine, New York University Langone Medical Center, New York, NY, USA;Department of Pathology, New York University Langone Medical Center, New York, NY, USA;Division of Neuropathology and Department of Neurosurgery, New York University School of Medicine, New York, NY, USA;New York University Cancer Institute, New York, NY, USA;Microvascular and Molecular Neuro-oncology laboratory, New York University School of Medicine, New York University Langone Medical Center, New York, NY, USA;Department of Pathology, New York University Langone Medical Center, New York, NY, USA;New York University Cancer Institute, New York, NY, USA;

关键词: Glioma Cell;    Cancer Stem Cell;    Hypoxic Condition;    Stem Cell Biology;    Tumor Sphere;   

DOI  :  10.1186/1476-4598-9-133

 received in 2009-11-02, accepted in 2010-06-01,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundGlioblastoma (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.ResultsTo further elucidate the functional role of HIF-1α in glioma cell migration in vitro and in invasion in vivo, 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 in vitro as well as their ability to invade into the brain parenchyma in vivo. 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 glioblastomasConclusionsOur data show that knock down of HIF-1α in human and murine glioma cells impairs their migration in vitro and their invasion in vivo. 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.

【 授权许可】

Unknown   
© Méndez et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.