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Aberrant self‐renewal and quiescence contribute to the aggressiveness of glioblastoma
Author(s) -
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,
HeroldMende Christel
Publication year - 2014
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.4366
Subject(s) - glioblastoma , cell culture , biology , cell division , stem cell , cell growth , cell , cell cycle , phenotype , cancer research , microbiology and biotechnology , permissive , neuroscience , genetics , gene
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.