Department of Hematology and Oncology, University of Regensburg, Germany.
Cell Mol Neurobiol. 2011 Apr;31(3):337-43. doi: 10.1007/s10571-010-9627-4. Epub 2010 Nov 17.
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(+)/telomerase(high) CSC give rise to non-tumorigenic, CD133(-)/telomerase(low) 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(-)/telomerase(low) progenitor cell population characterized by low telomerase activity and shortened telomeres as compared to CSC.
多形性胶质母细胞瘤（GBM）是研究实体瘤中癌症干细胞（CSC）的典型范例。CSC 假说表明，肿瘤由一小部分 CSC 维持，这些 CSC 产生快速增殖的祖细胞。尽管祖细胞的存在对 CSC 假说至关重要，但源自 GBM CSC 的祖细胞尚未得到表征。我们分析了直接源自 CD133(+)原发性星形胶质细胞瘤的人 CD133(+) CSC 系。在这些 CSC 系中，CD133(+)/端粒酶(高)CSC 产生非致瘤性的、CD133(-)/端粒酶(低)祖细胞。与包含 CSC 的 CD133(+) 区室相比，祖细胞群体的增殖导致显著的端粒缩短。通过改良的多色流式荧光原位杂交确定的端粒长度平均差异为 320bp，相当于 4-8 个细胞分裂。总之，我们证明 CD133(+)原发性星形胶质细胞瘤包含增殖性的、CD133(-)/端粒酶(低)祖细胞群体，其特征是与 CSC 相比端粒酶活性低，端粒缩短。
