The Role of White Matter Progenitors in Glioma Formation and Progression
Principal Investigator: Peter D Canoll
Abstract: DESCRIPTION (provided by applicant): The adult brain contains several distinct populations of cycling cells. Prominent among these is a large and widely distributed population of oligodendrocyte progenitor cells that express platelet derived growth factor receptor alpha (PDGFR1). Normally these cells are non-migratory and slowly proliferating. However, they can be induced to proliferate massively when stimulated with PDGF. We have shown that infecting glial progenitors in the adult subcortical white matter with retroviruses that express PDGF-B will induce the formation of brain tumors that have the histological features of malignant gliomas. These tumors are composed of a mixture of retrovirus infected progenitors and reactive progenitors that have been driven to proliferate by PDGF stimulation. Furthermore, genetically deleting tumor suppressor genes PTEN or p53 greatly facilitates PDGF driven proliferation and glioma formation. The goal of this proposal is to characterize the role(s) of adult glial progenitors play in the formation and progression of gliomas, both as genetically transformed cells and as reactive cells in the tumor environment. We believe these studies will provide important insight into the basic mechanism that drive gliomagenesis. PUBLIC HEALTH RELEVANCE: Oligodendrocyte progenitors are one of the largest populations of cycling cells in the adult brain. These cells have an inherent capacity to proliferate massively when stimulated with platelet derived growth factor (PDGF) and genetic deletion of the tumor suppressor genes PTEN and p53 greatly facilitate their responsiveness to PDGF. Our goal is to characterize the role that adult oligodendrocyte progenitors play in the formation and progression of malignant gliomas.
Funding Period: 2010-02-01 - 2015-01-31
more information: NIH RePORT
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Department of Neuropathology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Glia 58:1050-65. 2010..Together, these findings are the first implications regarding the cell-of-origin and the gliomagenesis in the brainstem...
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CNC Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra 3004 517, Portugal
Hum Mol Genet 21:5118-30. 2012..Overall, our findings suggest that, besides its role in inducing GBM tumorigenesis, PDGF-B may enhance tumor proliferation by modulating the expression of oncomiRs and tumor suppressor miRNAs in U87 human GBM cells...
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CNC Center for Neuroscience and Cell Biology, University of Coimbra, 3004 517 Coimbra, Portugal
Hum Mol Genet 22:904-18. 2013..Overall, our results provide evidence that miR-21 is uniformly overexpressed in GBM and constitutes a highly promising target for multimodal therapeutic approaches toward GBM...
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Gabriele Bartoli Brain Tumor Laboratory, Departments of Neurosurgery, Columbia University Medical Center, 1130 St Nicholas Avenue Room 1001, New York, NY 10032, USA
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Gabriele Bartoli Brain Tumor Laboratory, Department of Neurosurgery, Columbia University Medical Center, 1130 St Nicholas Ave Rm 1001, New York, NY 10032, USA
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The Gabriele Bartoli Brain Tumor Research Laboratory, Department of Neurological Surgery, The Neurological Institute, Columbia University College of Physicians and Surgeons, New York City, NY 10032, USA
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Division of Molecular Imaging and Neuropathology, Department of Psychiatry, Columbia University College of Physicians and Surgeons, NY, USA
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Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, New York, NY 10029, USA
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Department of Neurosurgery, Gabriele Bartoli Brain Tumor Research Laboratory, Columbia University, New York, New York, United States of America
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Authors Affiliations Gabriele Bartoli Brain Tumor Laboratory, Department of Neurosurgery Department of Pathology and Cell Biology, Columbia University Department of Biochemistry and Molecular Biophysics, Columbia University Medical Center Departments of Systems Biology and Biomedical Informatics Center for Computational Biology and Bioinformatics Institute for Cancer Genetics and Herbert Irving Comprehensive Cancer Center, Columbia University, New York, New York Department of Molecular and Cellular Biochemistry, The Ohio State University Medical Center, Columbus and Brain Tumor and Neuro Oncology Center, Cleveland Clinic, Cleveland, Ohio
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Center for Computational Biology and Bioinformatics, Columbia University, New York, New York, United States of America
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Department of Neurological Surgery, Columbia University College of Physicians and Surgeons, New York, New York, USA
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Department of Neuropathology, Graduate School of Medical Sciences, Kyushu University, 3 1 1 Maidashi, Higashi ku, Fukuoka 812 8582, Japan
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Department of Pathology and Cell Biology, Columbia University, New York, New York, United States of America
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Department of Neurological Surgery, Columbia University Medical Center, New York, New York 10032, USA
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Department of Neurological Surgery, Neurological Institute of New York, Columbia University Medical Center, 710 West 168th Street, New York, NY 10032, USA
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Department of Pathology and Cell Biology, Columbia University, NY 10032, USA
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Center for Computational Biology and Bioinformatics, Columbia University, New York, NY, USA
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Department of Neurology, Columbia University, New York, NY 10032, USA
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Department of Pathology, University of Washington, Box 357470, Seattle, WA 98195, USA
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Department of Biophysics, Columbia University Medical Center, New York, USA
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Departments of Neuroscience, Genetics and Genomics, and Medicine, Icahn School of Medicine at Mount Sinai, New York, New York 10029, Center for Neuroscience Research, Children s National Medical Center, George Washington University, Washington, DC 20010 2970, and Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York 10032
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