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Cancer Stem Cells Are Enriched in the Side Population Cells in a Mouse Model of Glioma

¹ The Jackson Laboratory, Bar Harbor, Maine; ² The Graduate School of Biomedical Sciences, University of Maine, Orono, Maine; ³ The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada; ⁴ Harvard Medical School, Department of Pathology, Boston, Massachusetts; and ⁵ Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire

Requests for reprints: Kyuson Yun, The Jackson Laboratory, 600 Main Street, Mailbox 76, Bar Harbor, ME 04609. Phone: 207-288-6825; Fax: 207-288-6078; E-mail: Kyuson.yun{at}jax.org.

Key Words: cancer stem cells • tumor-initiating cells • glioma • GBM • glioblastoma • mouse models • side population • SP cells

The recent identification of cancer stem cells (CSCs) in multiple human cancers provides a new inroad to understanding tumorigenesis at the cellular level. CSCs are defined by their characteristics of self-renewal, multipotentiality, and tumor initiation upon transplantation. By testing for these defining characteristics, we provide evidence for the existence of CSCs in a transgenic mouse model of glioma, S100β-verbB;Trp53. In this glioma model, CSCs are enriched in the side population (SP) cells. These SP cells have enhanced tumor-initiating capacity, self-renewal, and multipotentiality compared with non-SP cells from the same tumors. Furthermore, gene expression analysis comparing fluorescence-activated cell sorting–sorted cancer SP cells to non-SP cancer cells and normal neural SP cells identified 45 candidate genes that are differentially expressed in glioma stem cells. We validated the expression of two genes from this list (S100a4 and S100a6) in primary mouse gliomas and human glioma samples. Analyses of xenografted human glioblastoma multiforme cell lines and primary human glioma tissues show that S100A4 and S100A6 are expressed in a small subset of cancer cells and that their abundance is positively correlated to tumor grade. In conclusion, this study shows that CSCs exist in a mouse glioma model, suggesting that this model can be used to study the molecular and cellular characteristics of CSCs in vivo and to further test the CSC hypothesis. [Cancer Res 2008;68(24):10051–9]

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				Correction: Article on Cancer Stem Cells in Mouse Glioma Cancer Res., July 15, 2009; 69(14): 6005 - 6005. [Full Text] [PDF]