[Frontiers in Bioscience S4, 190-205, January 1, 2012]

The potential origin of glioblastoma initiating cells

David A. Chesler1,2,3, Mitchell S. Berger4, Alfredo Quinones-Hinojosa2,3

1Department of Neurosurgery, University of Maryland Medical Center, 22 S. Greene St., Suite 12-S-D, Baltimore, MD 21212, 2Department of Neurosurgery, Johns Hopkins School of Medicine, 1550 Orleans St, CRBII Room 247, Baltimore, MD 21231, 3Department of Oncology, Johns Hopkins School of Medicine, 1550 Orleans St, CRBII Room 247, Baltimore, MD 21231, 4Department of Neurosurgery, University of California San Francisco, 550 S. Parnassus Ave, Room 779 M, San Francisco, CA 94143

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Hypotheses regarding the cellular ontology of glioblastoma
4. Sources of neural stem cells and lineage-restricted progenitor cells in the post-natal mammalian brain
4.1. Organization of the Rodent Subventricular Zone
4.2. Organization of the Human Subventricular Zone
5. Malignant transformation of NSCs and lineage-restricted cells.
6. Similarities between NSCs and Glioma stem cells
6.1. Transcription factors
6.2 .Tumor suppressor genes
6.3. Growth factors / cytokines and their receptors
6.4. Vascular niche
6.5. Cytoskeletal proteins
7. Clinical evidence for the SVZ as a source of glioma initiating cells
8. Assigning a source for glioma initiating cells
9. Clinical Implications of glioma initiating cell identity
10. Conclusions
11. Acknowledgements
12. References

1. ABSTRACT

Despite intensive clinical and laboratory research and effort, Glioblastoma remains the most common and invariably lethal primary cancer of the central nervous system. The identification of stem cell and lineage-restricted progenitor cell populations within the adult human brain in conjunction with the discovery of stem-like cells derived from gliomas which are themselves tumorigenic and have been shown to have properties of self-renewal and multipotency, has led to the hypothesis that this population of cells may represent glioma initiating cells. Extensive research characterizing the anatomic distribution and phenotype of neural stem cells in the adult brain, and the genetic underpinnings needed for malignant transformation may ultimately lead to the identification of the cellular origin for glioblastoma. Defining the cellular origin of this lethal disease may ultimately provide new therapeutic targets and modalities finally altering an otherwise bleak outcome for patients with glioblastoma.