All-trans retinoic acid impairs the vasculogenic mimicry formation ability of U87 stem-like cells through promoting differentiation

Abstract

The poor therapeutic effect of traditional antiangiogenic therapy on glioblastoma multiforme (GBM) may be attributed to vasculogenic mimicry (VM), which was previously reported to be promoted by cancer stem-like cells (SLCs). All-trans retinoic acid (ATRA), a potent reagent which drives differentiation, was reported to be able to eradicate cancer SLCs in certain malignancies. The aim of the present study was to investigate the effects of ATRA on the VM formation ability of U87 glioblastoma SLCs. The expression of cancer SLC markers CD133 and nestin was detected using immunocytochemistry in order to identify U87 SLCs. In addition, the differentiation of these SLCs was observed through detecting the expression of glial fibrillary acidic protein (GFAP), β-tubulin III and galactosylceramidase (Galc) using immunofluorescent staining. The results showed that the expression levels of GFAP, β-tubulin III and Galc were upregulated following treatment with ATRA in a dose-dependent manner. Furthermore, ATRA significantly reduced the proliferation, invasiveness, tube formation and vascular endothelial growth factor (VEGF) secretion of U87 SLCs. In conclusion, the VM formation ability of SLCs was found to be negatively correlated with differentiation. These results therefore suggested that ATRA may serve as a promising novel agent for the treatment of GBM due to its role in reducing VM formation.