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Cancers 2011, 3(2), 1975-1995; doi:10.3390/cancers3021975

Essential Gene Pathways for Glioblastoma Stem Cells: Clinical Implications for Prevention of Tumor Recurrence

1
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
2
Department of Neurosurgery, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA
3
Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, California, USA
*
Author to whom correspondence should be addressed.
Received: 5 February 2011 / Revised: 19 February 2011 / Accepted: 22 March 2011 / Published: 18 April 2011
(This article belongs to the Special Issue Cancer Stem Cells)
View Full-Text   |   Download PDF [1548 KB, uploaded 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. View Full-Text
Keywords: glioblastoma; cancer stem cells; radial glial cells; neural crest cells; neural stem cells; radio-chemoresistance glioblastoma; cancer stem cells; radial glial cells; neural crest cells; neural stem cells; radio-chemoresistance
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

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.

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