Differentiation Therapy Exerts Antitumor Effects on Stem-like Glioma Cells

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

来源：Clinical Cancer Research, 2010, 16(10): 2715-2728.

DOI：10.1158/1078-0432.CCR-09-1800

• TRANS-RETINOIC ACID
• IN-VITRO
• GENE-EXPRESSION
• MARKER CD133
• PPAR-GAMMA
• CANCER
• GROWTH
• INHIBITION
• RECEPTORS
• APOPTOSIS

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.

• 出版日期2010-5-15
• 单位华中科技大学