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The Journal of Neuroscience, November 29, 2006, 26(48):12544-12555; doi:10.1523/JNEUROSCI.0829-06.2006
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Neurobiology of Disease
Neurocytoma Is a Tumor of Adult Neuronal Progenitor Cells
Fraser J. Sim,1 * H. Michael Keyoung,2 * James E. Goldman,3 Dong Kyu Kim,4 Hee-Won Jung,4 Neeta S. Roy,2 andSteven A. Goldman1,2 1Department of Neurology, University of Rochester Medical Center, Rochester, New York 14642, 2Department of Neurology, Weill Medical College of Cornell University, New York, New York 10021, 3Department of Pathology, Columbia University Medical School, New York, New York 10032, and 4Department of Neurosurgery, Seoul National University, Seoul 110-744, Korea
Correspondence should be addressed to Dr. Steven A. Goldman, Division of Cell and Gene Therapy, Department of Neurology, University of Rochester Medical Center, 601 Elmwood Avenue/MRBX Box 645, Rochester, NY 14642. Email: steven_goldman{at}urmc.rochester.edu
Central neurocytoma (CN) is a rare periventricular tumor, whose derivation, lineage potential, and molecular regulation have been mostly unexplored. We noted that CN cells exhibited an antigenic profile typical of neuronal progenitor cells in vivo, yet in vitro generated neurospheres, divided in response to bFGF (basic fibroblast growth factor), activated the neuroepithelial enhancer of the nestin gene, and gave rise to both neuron-like cells and astrocytes. When CN gene expression was compared with that of both normal adult VZ (ventricular zone) and E/nestin:GFP (green fluorescent protein)-sorted native neuronal progenitors, significant overlap was noted. Marker analysis suggested that the gene expression pattern of CN was that of a proneuronal population; glial markers were conspicuously absent, suggesting that the emergence of astroglia from CN occurred only with passage. The expression pattern of CN was distinguished from that of native progenitor cells by a cohort of differentially expressed genes potentially involved in both the oncogenesis and phenotypic restriction of neurocytoma. These included both IGF2 and several components of its signaling pathway, whose sharp overexpression implicated dysregulated autocrine IGF2 signaling in CN oncogenesis. Both receptors and effectors of canonical wnt signaling, as well as GDF8 (growth differentiation factor 8), PDGF-D, and neuregulin, were differentially overexpressed by CN, suggesting that CN is characterized by the concurrent overactivation of these pathways, which may serve to drive neurocytoma expansion while restricting tumor progenitor phenotype. This strategy of comparing the gene expression of tumor cells to that of the purified native progenitors from which they derive may provide a focused approach to identifying transcripts important to stem and progenitor cell oncogenesis.
Key words: brain tumor; neural stem cell; tumor stem cell; ventricular zone; oncogenomics; expression profile
Received Feb. 23, 2006; revised Aug. 28, 2006; accepted Sept. 17, 2006.
Correspondence should be addressed to Dr. Steven A. Goldman, Division of Cell and Gene Therapy, Department of Neurology, University of Rochester Medical Center, 601 Elmwood Avenue/MRBX Box 645, Rochester, NY 14642. Email: steven_goldman{at}urmc.rochester.edu
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[Abstract] [Full Text] [PDF]
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