期刊
STEM CELLS AND DEVELOPMENT
卷 17, 期 1, 页码 173-184出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/scd.2007.0133
关键词
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资金
- NCI NIH HHS [5 P30 CA077598, 1R41CA126014-01] Funding Source: Medline
- NINDS NIH HHS [1R21-NS055738-01A2] Funding Source: Medline
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 (similar to 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.
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