Journal article
Candidate Pathways for Promoting Differentiation or Quiescence of Oligodendrocyte Progenitor-like Cells in Glioma
Cancer research (Chicago, Ill.), v 72(18), pp 4856-4868
15 Sep 2012
PMID: 22865458
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Platelet-derived growth factor receptor alpha-positive oligodendrocyte progenitor cells (OPC) located within the mature central nervous system may remain quiescent, proliferate, or differentiate into oligodendrocytes. Human glioblastoma multiforme tumors often contain rapidly proliferating oligodendrocyte lineage transcription factor 2 (Olig2)-positive cells that resemble OPCs. In this study, we sought to identify candidate pathways that promote OPC differentiation or quiescence rather than proliferation. Gene expression profiling conducted in both normal murine OPCs and highly proliferative Olig2-positive glioma cells identified all the transcripts associated with the highly proliferative state of these cells and showed that among the various cell types found within the brain, Olig2-positive tumor cells are most similar to OPCs. We then subtracted OPC transcripts found in tumor samples from those found in normal brain samples and identified 28 OPC transcripts as candidates for promoting differentiation or quiescence. Systematic analysis of human glioma data revealed that these genes have similar expression profiles in human tumors and were significantly enriched in genomic deletions, suggesting an antiproliferative role. Treatment of primary murine glioblastoma cells with agonists of one candidate gene, Gpr17, resulted in a decreased number of neurospheres. Together, our findings show that comparison of the molecular phenotype of progenitor cells in tumors to the equivalent cells in the normal brain represents a novel approach for the identification of targeted therapies. Cancer Res; 72(18); 4856-68. (C)2012 AACR.
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Details
- Title
- Candidate Pathways for Promoting Differentiation or Quiescence of Oligodendrocyte Progenitor-like Cells in Glioma
- Creators
- Joseph D. Dougherty - Rockefeller UniversityElena I. Fomchenko - Rockefeller UniversityAfua A. Akuffo - Rockefeller UniversityEric Schmidt - Rockefeller UniversityKarim Y. Helmy - Memorial Sloan Kettering Cancer CenterElena Bazzoli - Rockefeller UniversityCameron W. Brennan - Memorial Sloan Kettering Cancer CenterEric C. Holland - Memorial Sloan Kettering Cancer CenterAna Milosevic - Rockefeller University
- Publication Details
- Cancer research (Chicago, Ill.), v 72(18), pp 4856-4868
- Publisher
- Amer Assoc Cancer Research
- Number of pages
- 13
- Grant note
- R00NS067239 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) Adelson Medical Research Foundation Tri-Institutional Stem Cell Initiative award 4R00NS067239-03 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA U54CA163167 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurology
- Web of Science ID
- WOS:000309507900027
- Scopus ID
- 2-s2.0-84866369083
- Other Identifier
- 991022004951604721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Oncology