Candidate pathways for promoting differentiation or quiescence of oligodendrocyte progenitor-like cells in glioma Journal Article
| Authors: | Dougherty, J. D.; Fomchenko, E. I.; Akuffo, A. A.; Schmidt, E.; Helmy, K. Y.; Bazzoli, E.; Brennan, C. W.; Holland, E. C.; Milosevic, A. |
| Article Title: | Candidate pathways for promoting differentiation or quiescence of oligodendrocyte progenitor-like cells in glioma |
| 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 pro files 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. ©2012 AACR. |
| Keywords: | signal transduction; human tissue; gene deletion; nonhuman; glioma; brain neoplasms; cell proliferation; animal cell; mouse; phenotype; animals; mice; animal tissue; gene; gene expression profiling; cell differentiation; in vitro study; stem cell; neoplastic stem cells; microarray analysis; glioma cell; cellular distribution; stem cells; transcriptome; cell activity; quiescence; intracellular signaling; molecularly targeted therapy; antiproliferative activity; oligodendroglia; brain tissue; gpr17 gene; oligodendrocyte progenitor like cell |
| Journal Title: | Cancer Research |
| Volume: | 72 |
| Issue: | 18 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2012-09-15 |
| Start Page: | 4856 |
| End Page: | 4868 |
| Language: | English |
| DOI: | 10.1158/0008-5472.can-11-2632 |
| PROVIDER: | scopus |
| PUBMED: | 22865458 |
| PMCID: | PMC3543775 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 October 2012" - "CODEN: CNREA" - "Source: Scopus" |
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