Persistence of CD133+ cells in human and mouse glioma cell lines: Detailed characterization of GL261 glioma cells with cancer stem cell-like properties

Anhua Wu, Seunguk Oh, Stephen M. Wiesner, Katya Ericson, Lisa Chen, Walter A. Hall, Paul E. Champoux, Walter C. Low, John R. Ohlfest

Research output: Contribution to journalArticle

94 Scopus citations

Abstract

The concept of cancer stem cells suggests that there are malignant stem-like cells within a tumor that are responsible for tumor renewal and resistance to cytotoxic therapies. Studies have identified glioma stem-like cells that extrude Hoechst 33342 dye, representing a double-negative "side population" (SP) thought to be selectively resistant to drug therapy. A CD133+ stem cell-like subpopulation has been isolated from a human glioma that was enriched for tumor-initiating cells. It is unknown whether CD133+ cells with similar phenotype persist in established glioma cell lines, or if CD133 is a marker of glioma stem-like cells in rodents. We investigated whether CD133+ and SP cells existed in the GL261 cell line, a syngeneic mouse glioma model that is widely used for preclinical and translational research. Intracerebral injection of less than 100 CD133 + GL261 cells formed tumors, whereas it required 10,000 CD133 - cells to initiate a tumor. CD133+ GL261 cells expressed nestin, formed tumor spheres with high frequency, and differentiated into glial and neuronal-like cells. Similar to GL261, seven human glioma cell lines analyzed also contained a rare CD133+ population. Surprisingly, we found that CD133+ GL261 cells did not reside in the SP, nor did the majority (∼94%) of CD133+ human glioma cells. These results demonstrate that the expression of CD133 in murine glioma cells is associated with enhanced tumorigenicity and a stem-like phenotype. This study also reveals a previously unrecognized level of heterogeneity in glioma cell lines, exposing several populations of cells that have characteristics of cancer stem cells.

Original languageEnglish (US)
Pages (from-to)173-184
Number of pages12
JournalStem Cells and Development
Volume17
Issue number1
DOIs
StatePublished - Feb 1 2008

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