Differentiation therapy exerts antitumor effects on stem-like glioma cells

Benito Campos, Feng Wan, Mohammad Farhadi, Aurélie Ernst, Felix Zeppernick, Katrin E. Tagscherer, Rezvan Ahmadi, Jennifer Lohr, Christine Dictus, Georg Gdynia, Stephanie E. Combs, Violaine Goidts, Burkhard M. Helmke, Volker Eckstein, Wilfried Roth, Philipp Beckhove, Peter Lichter, Andreas Unterberg, Bernhard Radlwimmer, Christel Herold-Mende

Research output: Contribution to journalArticlepeer-review

257 Scopus citations

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.

Original languageEnglish
Pages (from-to)2715-2728
Number of pages14
JournalClinical Cancer Research
Volume16
Issue number10
DOIs
StatePublished - 15 May 2010
Externally publishedYes

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