Abstract
The aim of this study was to investigate the mechanisms and effects of B-cell lymphoma 2 (Bcl-2) on the vasculogenic mimicry (VM) of human glioma cells. U87 cells were cultured under hypoxic conditions and then divided into four groups: Control, 3-(5-hydroxymethyl-2-furyl)-1-benzylindazole (YC-1), ABT-737 and YC-1 + ABT-737. These groups were treated with the corresponding simulators. The expression of hypoxia-inducible factor-1α (HIF-1α), matrix metalloproteinase (MMP)-2, MMP-14 and Bcl-2 in each group was determined using a reverse transcription-quantitative polymerase chain reaction and western blot analysis. Compared with that in the control group, the mRNA and protein expression of MMP-2, MMP-14 and Bcl-2 in the YC-1 and ABT-737 groups was significantly reduced. The expression of HIF-1α, however, was only significantly reduced in the YC-1 group (P<0.05). Compared with those in the YC-1 + ABT-737 group, the expression levels of the four proteins in the YC-1 and ABT-737 groups were not significantly different, with the exception of the expression of HIF-1α in the ABT-737 group, which was significantly enhanced (P<0.05). The mRNA expression levels of HIF-1α, MMP-2 and MMP-14 in the YC-1 group were significantly different from those in the ABT-737 group (P<0.01); however, no significant difference was observed in the expression of Bcl-2. In conclusion, Bcl-2 may be an important factor in the VM formation of human malignant glioma U87 cells under hypoxic conditions. Certain functions of Bcl-2 may be attributed to the HIF-1α-MMP-2-MMP-14-VM channel, whereas other functions may be independent of the channel.
Highlights
Vasculogenic mimicry (VM) is a unique blood supply pattern present in malignant tumours
VM refers to the remodelling of tumour cells into a luminal‐like structure for blood flow, no endothelial cells are present on the inner luminal surface
Hypoxia‐inducible factor‐1α (HIF‐1α)‐vascular endothelial growth factor (VEGF)‐Ephrin type‐A receptor 2 (EphA2)‐matrix metalloproteinase (MMP)‐VM may be a key channel for VM formation under hypoxic conditions
Summary
Vasculogenic mimicry (VM) is a unique blood supply pattern present in malignant tumours. VM refers to the remodelling of tumour cells into a luminal‐like structure for blood flow, no endothelial cells are present on the inner luminal surface. The mechanisms underlying its formation remain unclear, but a variety of proteins and microenvironmental factors are known to contribute to VM [2,3,4]. Inducing hypoxic conditions can promote the biological behaviour and VM of malignant glioma (SHG‐44) cells. Hypoxia‐inducible factor‐1α (HIF‐1α)‐vascular endothelial growth factor (VEGF)‐Ephrin type‐A receptor 2 (EphA2)‐matrix metalloproteinase (MMP)‐VM may be a key channel for VM formation under hypoxic conditions. In addition to HIF‐1α and VEGF, which contribute to the mechanisms of VM formation, another known factor that promotes the VM formation of highly malignant glioma cells is the hypoxic condition [7,8]. The 3‐(5‐hydroxymethyl‐2‐furyl)‐1‐benzylindazole (YC‐1)‐induced inhibition of HIF‐1α has been found to downregulate the VM formation of glioma cells [9] under hypoxic conditions; other pathways, aside from the HIF‐1α pathway, may affect the VM formation of glioma cells [10,11,12]
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