title: 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.
authors.affiliation: Department of Neurosurgery, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
authors.forename: Geng-Qiang
authors.initials: GQ
authors.lastname: Ling
authors.affiliation: Department of Neurosurgery, Zhujiang Hospital, National Key Clinic Department, Neurosurgery Institute, Key Laboratory on Brain Function Repair and Regeneration of Guangdong, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.
authors.forename: Yi-Jing
authors.initials: YJ
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Zhujiang Hospital, National Key Clinic Department, Neurosurgery Institute, Key Laboratory on Brain Function Repair and Regeneration of Guangdong, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.
authors.forename: Yi-Quan
authors.initials: YQ
authors.lastname: Ke
authors.affiliation: Department of Neurosurgery, Zhujiang Hospital, National Key Clinic Department, Neurosurgery Institute, Key Laboratory on Brain Function Repair and Regeneration of Guangdong, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Zhujiang Hospital, National Key Clinic Department, Neurosurgery Institute, Key Laboratory on Brain Function Repair and Regeneration of Guangdong, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.
authors.forename: Xiao-Dan
authors.initials: XD
authors.lastname: Jiang
authors.affiliation: Department of Neurosurgery, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
authors.forename: Chuan-Lu
authors.initials: CL
authors.lastname: Jiang
authors.affiliation: Department of Neurosurgery, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ye
mesh_terms: D000071916:AC133 Antigen; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005698:Galactosylceramidase / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D005904:Glial Fibrillary Acidic Protein / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D064231:Nestin / Q000235:genetics / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D014404:Tubulin / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D000071916:AC133 Antigen; D020533:Angiogenesis Inhibitors; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D005904:Glial Fibrillary Acidic Protein; D006023:Glycoproteins; C577484:NES protein, human; D064231:Nestin; C000606023:PROM1 protein, human; D010455:Peptides; C498585:TUBB3 protein, human; D014404:Tubulin; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D014212:Tretinoin; D005698:Galactosylceramidase