PT  - JOURNAL ARTICLE
AU  - Campos, Benito
AU  - Wan, Feng
AU  - Farhadi, Mohammad
AU  - Ernst, Aurélie
AU  - Zeppernick, Felix
AU  - Tagscherer, Katrin E.
AU  - Ahmadi, Rezvan
AU  - Lohr, Jennifer
AU  - Dictus, Christine
AU  - Gdynia, Georg
AU  - Combs, Stephanie E.
AU  - Goidts, Violaine
AU  - Helmke, Burkhard M.
AU  - Eckstein, Volker
AU  - Roth, Wilfried
AU  - Beckhove, Philipp
AU  - Lichter, Peter
AU  - Unterberg, Andreas
AU  - Radlwimmer, Bernhard
AU  - Herold-Mende, Christel
TI  - Differentiation Therapy Exerts Antitumor Effects on Stem-like Glioma Cells
AID  - 10.1158/1078-0432.CCR-09-1800
DP  - 2010 May 15
TA  - Clinical Cancer Research
PG  - 2715--2728
VI  - 16
IP  - 10
4099  - http://clincancerres.aacrjournals.org/content/16/10/2715.short
4100  - http://clincancerres.aacrjournals.org/content/16/10/2715.full
SO  - Clin Cancer Res2010 May 15; 16
AB  - 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. Clin Cancer Res; 16(10); 2715–28. ©2010 AACR.