期刊
CLINICAL CANCER RESEARCH
卷 16, 期 10, 页码 2715-2728出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-09-1800
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资金
- Sibylle Assmus Foundation
- Helmholtz Society [NT-GE-016+062]
- Verein zur Forderung der Krebsforschung
- Heinz Goetze Memorial Fellowship Program
- Bundesministerium fur Bildung und Forschung [01GS0886]
- Tumorzentrum Heidelberg/Mannheim
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. (C) 2010 AACR.
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