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Clin Cancer Res. 2010 May 15;16(10):2715-28. doi: 10.1158/1078-0432.CCR-09-1800. Epub 2010 May 4.

Differentiation therapy exerts antitumor effects on stem-like glioma cells.

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  • 1Division of Neurosurgical Research, Department of Neurosurgery, University of Heidelberg, Heidelberg, Germany.

Abstract

PURPOSE:

Stem-like tumor cells comprise a highly tumorigenic and therapy-resistant tumor subpopulation, which is believed to substantially influence tumor initiation and therapy resistance in glioma. Currently, therapeutic, drug-induced differentiation is considered as a promising approach to eradicate this tumor-driving cell population; retinoic acid is well known as a potent modulator of differentiation and proliferation in normal stem cells. In glioma, knowledge about the efficacy of retinoic acid-induced differentiation to target the stem-like tumor cell pool could have therapeutic implications.

EXPERIMENTAL DESIGN:

Stem-like glioma cells (SLGC) were differentiated with all-trans retinoic acid-containing medium to study the effect of differentiation on angiogenesis, invasive growth, as well as radioresistance and chemoresistance of SLGCs. In vivo effects were studied using live microscopy in a cranial window model.

RESULTS:

Our data suggest that in vitro differentiation of SLGCs induces therapy-sensitizing effects, impairs the secretion of angiogenic cytokines, and disrupts SLGCs motility. Further, ex vivo differentiation reduces tumorigenicity of SLGCs. Finally, we show that all-trans retinoic acid treatment alone can induce antitumor effects in vivo.

CONCLUSIONS:

Altogether, these results highlight the potential of differentiation treatment to target the stem-like cell population in glioblastoma.

Copyright (c) 2010 AACR.

PMID:
20442299
[PubMed - indexed for MEDLINE]
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