Aberrant self-renewal and quiescence contribute to the aggressiveness of glioblastoma

Cancer cells with enhanced self‐renewal capacity influence tumour growth in glioblastoma. So far, a variety of surrogate markers have been proposed to enrich these cells, emphasizing the need to devise new characterization methods. Here, we screen a large panel of glioblastoma cultures (n = 21) cult...

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Bibliographic Details
Published in:The Journal of pathology 2014-09, Vol.234 (1), p.23-33
Main Authors: Campos, Benito, Gal, Zoltan, Baader, Aline, Schneider, Tilman, Sliwinski, Christopher, Gassel, Kristina, Bageritz, Josephine, Grabe, Niels, von Deimling, Andreas, Beckhove, Philipp, Mogler, Carolin, Goidts, Violaine, Unterberg, Andreas, Eckstein, Volker, Herold-Mende, Christel
Format: Article
Language:English
Subjects:
Animals
Brain Neoplasms - metabolism
Brain Neoplasms - pathology
Cell Line, Tumor
Cell Proliferation
Comparative Genomic Hybridization
Disease Models, Animal
Gene Dosage - genetics
Gene Expression Profiling
glioblastoma
Glioblastoma - metabolism
Glioblastoma - pathology
Humans
label retention
Mice
Neoplasm Recurrence, Local - pathology
Neoplastic Stem Cells - metabolism
Neoplastic Stem Cells - pathology
Oligonucleotide Array Sequence Analysis
quiescence
self-renewal
self‐renewal
glioblastoma
label retention
quiescence
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Summary:Cancer cells with enhanced self‐renewal capacity influence tumour growth in glioblastoma. So far, a variety of surrogate markers have been proposed to enrich these cells, emphasizing the need to devise new characterization methods. Here, we screen a large panel of glioblastoma cultures (n = 21) cultivated under stem cell‐permissive conditions and identify several cell lines with enhanced self‐renewal capacity. These cell lines are capable of matrix‐independent growth and form fast‐growing, orthotopic tumours in mice. Employing isolation, re‐plating, and label‐retention techniques, we show that self‐renewal potential of individual cells is partitioned asymmetrically between daughter cells in a robust and cell line‐specific fashion. This yields populations of fast‐ and slow‐cycling cells, which differ in the expression of cell cycle‐associated transcripts. Intriguingly, fast‐growing cells keep their slow‐cycling counterparts in a reversible state of quiescence associated with high chemoresistance. Our results suggest that two different subpopulations of tumour cells contribute to aberrant growth and tumour recurrence after therapy in glioblastoma. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
ISSN:0022-3417
1096-9896
DOI:10.1002/path.4366