Abstract
Glioblastoma multiforme (GBM) is paradigmatic for the investigation of cancer stem cells (CSC) in solid tumors. The CSC hypothesis implies that tumors are maintained by a rare subpopulation of CSC that gives rise to rapidly proliferating progenitor cells. Although the presence of progenitor cells is crucial for the CSC hypothesis, progenitor cells derived from GBM CSC are yet uncharacterized. We analyzed human CD133+ CSC lines that were directly derived from CD133+ primary astrocytic GBM. In these CSC lines, CD133+/telomerasehigh CSC give rise to non-tumorigenic, CD133−/telomeraselow progenitor cells. The proliferation of the progenitor cell population results in significant telomere shortening as compared to the CD133+ compartment comprising CSC. The average difference in telomere length as determined by a modified multi-color flow fluorescent in situ hybridization was 320 bp corresponding to 4–8 cell divisions. Taken together, we demonstrate that CD133+ primary astrocytic GBM comprise proliferating, CD133−/telomeraselow progenitor cell population characterized by low telomerase activity and shortened telomeres as compared to CSC.
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Acknowledgments
We would like to thank Gunnar Müller and Elena Spacenko for their excellent technical assistance. This work was supported by the Reform A grant of the University of Regensburg, the NGFNplus Brain Tumor Network (Subproject 7 no. 01GS0887), and the Max Eder grant of the Deutsche Krebshilfe e.V.
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Fabian Beier and Christoph P. Beier equally contributed to this study.
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Beier, F., Beier, C.P., Aschenbrenner, I. et al. Identification of CD133−/Telomeraselow Progenitor Cells in Glioblastoma-Derived Cancer Stem Cell Lines. Cell Mol Neurobiol 31, 337–343 (2011). https://doi.org/10.1007/s10571-010-9627-4
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DOI: https://doi.org/10.1007/s10571-010-9627-4