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Essential Gene Pathways for Glioblastoma Stem Cells: Clinical Implications for Prevention of Tumor Recurrence
Department of Surgery/Surgical Oncology, David Geffen School of Medicine, University of California Los Angeles, 13-260 Factor building, 10833 Le Conte Avenue, Los Angeles, California 90095, USA
Department of Neurosurgery, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA
Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, California, USA
* Author to whom correspondence should be addressed.
Received: 5 February 2011; in revised form: 19 February 2011 / Accepted: 22 March 2011 / Published: 18 April 2011
Abstract: Glioblastoma (World Health Organization/WHO grade IV) is the most common and most aggressive adult glial tumor. Patients with glioblastoma, despite being treated with gross total resection and post-operative radiation/chemotherapy, will almost always develop tumor recurrence. Glioblastoma stem cells (GSC), a minor subpopulation within the tumor mass, have been recently characterized as tumor-initiating cells and hypothesized to be responsible for post-treatment recurrence because of their enhanced radio-/chemo-resistant phenotype and ability to reconstitute tumors in mouse brains. Genome-wide expression profile analysis uncovered molecular properties of GSC distinct from their differentiated, proliferative progeny that comprise the majority of the tumor mass. In contrast to the hyperproliferative and hyperangiogenic phenotype of glioblastoma tumors, GSC possess neuroectodermal properties and express genes associated with neural stem cells, radial glial cells, and neural crest cells, as well as portray a migratory, quiescent, and undifferentiated phenotype. Thus, cell cycle-targeted radio-chemotherapy, which aims to kill fast-growing tumor cells, may not completely eliminate glioblastoma tumors. To prevent tumor recurrence, a strategy targeting essential gene pathways of GSC must be identified and incorporated into the standard treatment regimen. Identifying intrinsic and extrinsic cues by which GSC maintain stemness properties and sustain both tumorigenesis and anti-apoptotic features may provide new insights into potentially curative strategies for treating brain cancers.
Keywords: glioblastoma; cancer stem cells; radial glial cells; neural crest cells; neural stem cells; radio-chemoresistance
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Yamada, K.; Tso, J.; Ye, F.; Choe, J.; Liu, Y.; Liau, L.M.; Tso, C.-L. Essential Gene Pathways for Glioblastoma Stem Cells: Clinical Implications for Prevention of Tumor Recurrence. Cancers 2011, 3, 1975-1995.
Yamada K, Tso J, Ye F, Choe J, Liu Y, Liau LM, Tso C-L. Essential Gene Pathways for Glioblastoma Stem Cells: Clinical Implications for Prevention of Tumor Recurrence. Cancers. 2011; 3(2):1975-1995.
Yamada, Kazunari; Tso, Jonathan; Ye, Fei; Choe, Jinny; Liu, Yue; Liau, Linda M.; Tso, Cho-Lea. 2011. "Essential Gene Pathways for Glioblastoma Stem Cells: Clinical Implications for Prevention of Tumor Recurrence." Cancers 3, no. 2: 1975-1995.