title: Identification of CD133(-)/telomerase(low) progenitor cells in glioblastoma-derived cancer stem cell lines.
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(+)/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.
authors.affiliation: Department of Hematology and Oncology, University of Regensburg, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Beier
authors.forename: Christoph P
authors.initials: CP
authors.lastname: Beier
authors.forename: Ines
authors.initials: I
authors.lastname: Aschenbrenner
authors.forename: Gerhard C
authors.initials: GC
authors.lastname: Hildebrandt
authors.forename: Tim H
authors.initials: TH
authors.lastname: Brümmendorf
authors.forename: Dagmar
authors.initials: D
authors.lastname: Beier
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005909:Glioblastoma / Q000201:enzymology* / Q000473:pathology*; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000201:enzymology* / Q000502:physiology; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D019098:Telomerase