The Role of White Matter Progenitors in Glioma Formation and Progression

Columbia University Health Sciences, New York NY

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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.