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Cancer Stem Cells
Article first published online: 5 APR 2011
Copyright © 2011 AlphaMed Press
Volume 29, Issue 4, pages 590–599, April 2011
How to Cite
Hide, T., Takezaki, T., Nakatani, Y., Nakamura, H., Kuratsu, J.-i. and Kondo, T. (2011), Combination of a Ptgs2 Inhibitor and an Epidermal Growth Factor Receptor-Signaling Inhibitor Prevents Tumorigenesis of Oligodendrocyte Lineage-Derived Glioma-Initiating Cells. STEM CELLS, 29: 590–599. doi: 10.1002/stem.618
Disclosure of potential conflicts of interest is found at the end of this article.
Author contributions: T.H.: conception and design, data collection, data analysis and interpretation, manuscript writing; T.T.: data collection, data analysis and interpretation; Y.N.: data collection and analysis; H.N.: provision of study material; J.-I.K.: financial support, provision of study material; T.K.: conception and design, data analysis and interpretation, manuscript writing, financial support, final approval of manuscript.
First published online in STEM CELLSEXPRESS February 25, 2011.
- Issue published online: 5 APR 2011
- Article first published online: 5 APR 2011
- Accepted manuscript online: 25 FEB 2011 03:01PM EST
- Manuscript Accepted: 26 JAN 2011
- Manuscript Received: 1 JUN 2009
- Grant-In-Aid for Scientific Research
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Neural stem cells;
- Oligodendrocyte precursor cells;
- Glioma-initiating cells
Recent findings have demonstrated that malignant tumors, including glioblastoma multiforme (GBM), contain cancer-initiating cells (CICs; also known as cancer stem cells), which self-renew and are malignant. However, it remains controversial whether such CICs arise from tissue-specific stem cells, committed precursor cells, or differentiated cells. Here, we sought to examine the origin of the CICs in GBM. We first showed that the overexpression of oncogenic HRasL61 transformed p53-deficient oligodendrocyte precursor cells (OPCs) and neural stem cells (NSCs) into glioma-initiating cell (GIC)-like cells in mice. When as few as 10 of these GIC-like cells were transplanted in vivo, they formed a transplantable GBM with features of human GBM, suggesting that these GIC-like cells were enriched in CICs. DNA microarray analysis showed that widespread genetic reprogramming occurred during the OPCs' transformation: they largely lost their OPC characteristics and acquired NSC ones, including the expression of prominin1, hmga2, ptgs2, and epiregulin. In addition, the combination of a Ptgs2 inhibitor and an epidermal growth factor receptor (EGFR)-signaling inhibitor prevented the tumorigenesis of transformed OPCs and human GICs (hGICs) obtained from anaplastic oligodendroglioma, but not of transformed NSCs or hGICs obtained from GBM. Together, these findings suggest that GBM can arise from either OPCs or NSCs and that the therapeutic targets for GBM might be different, depending on each GIC's cell-of-origin. STEM Cells 2011;29:590–599