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) 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.
Experimental Neurosurgery, Department of Neurosurgery, University of Heidelberg, INF 400, 69120, Heidelberg, Germany.
Benito
B
Campos
Zoltan
Z
Gal
Aline
A
Baader
Tilman
T
Schneider
Christopher
C
Sliwinski
Kristina
K
Gassel
Josephine
J
Bageritz
Niels
N
Grabe
Andreas
A
von Deimling
Philipp
P
Beckhove
Carolin
C
Mogler
Violaine
V
Goidts
Andreas
A
Unterberg
Volker
V
Eckstein
Christel
C
Herold-Mende
D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D055028:Comparative Genomic Hybridization; D004195:Disease Models, Animal; D018628:Gene Dosage / Q000235:genetics; D020869:Gene Expression Profiling; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D051379:Mice; D009364:Neoplasm Recurrence, Local / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis
self-renewal; glioblastoma; label retention; quiescence