缺氧诱导SHG44细胞拟态血管形成及相关机制  

Formation and mechanism of vasculogenic mimicry induced by hypoxia in human astrocytoma SHG44 cells

作　　者：张熙[1] 郭世文[1] 尉春艳[2] 

机构地区：[1]西安交通大学医学院第一附属医院神经外科,陕西西安710061 [2]西安交通大学医学院第二附属医院妇产科,陕西西安710004

出　　处：《中华神经外科疾病研究杂志》2011年第3期218-221,共4页Chinese Journal of Neurosurgical Disease Research

基　　金：国家自然科学基金资助项目(30672126)

摘　　要：目的探索缺氧对Ⅱ-Ⅲ级人脑星形细胞瘤细胞血管生成拟态(VM)的诱导作用及其相关机制。方法应用化学缺氧法诱导人脑星形细胞瘤SHG44细胞(Ⅱ-Ⅲ级)在三维培养体系中形成血管生成拟态,采用Transwell法检测细胞的迁移和侵袭能力,用Western blot和逆转录聚合酶链反应(RT-PCR)检测血管内皮生长因子(VEGF)、酪氨酸蛋白激酶受体A2(EphA2)、基质金属蛋白酶2(MMP2)、MMP9和血管内皮钙粘蛋白(VE-cadherin)的表达,探讨缺氧诱导血管生成拟态的机制。结果在三维培养体系中,缺氧能诱导SHG44细胞相互连接,相互融合形成管状结构。缺氧组平均每视野管状结构数量为56.80±12.21,对照组为4.20±2.62,两组相比具有统计学差异(P<0.01)。缺氧组细胞侵袭数目为64.56±16.40,细胞迁移数目为178.71±18.81,明显高于对照组(P<0.01),与血管生成拟态的形成呈正相关。VEGF、EphA2、MMP2、MMP9的表达也明显增强,但是VE-cadherin的表达无明显改变。结论缺氧能够诱导SHG44细胞形成血管生成拟态,VEGF-EphA2-MMPs-VM可能是形成血管生成拟态的关键通路。Objective To investigate the vasculogenic mimicry（VM） formation induced by hypoxia in grade Ⅱ~Ⅲ human astrocytoma SHG44 cells and its mechanism.Methods VM of SHG44 cells in three-dimensional culture was induced by CoCl2.The migration and invasion of SHG44 cells was detected by Transwell assay.Western blot and RT-PCR were used to detect the expressions of vascular endothelial growth factor（VEGF）,tyrosine protein kinase receptor A2（EphA2）,matrix metalloproteinase 2（MMP2）,matrix metalloproteinase 9（MMP9） and vascular-endothelial（VE）-cadherin to investigate the mechanism.Results In three-dimensional culture under hypoxic condition,SHG44 cells remolded and linked each other to form wreath and net-work structure.The number of VM was 56.80±12.21 in hypoxia group and 4.20±2.62 in control group with significant difference（P0.01）.The numbers of cell invasion and cell migration was 64.56±16.40 and 178.71±18.81 in hypoxia group respectively,which were significant higher than that in control group（P0.01） and positively correlated with the number of VM.The expressions of VEGF,EphA2,MMP2 and MMP9 in hypoxia group were significantly higher than that in control group.But there was no obvious change of VE-cadherin expression.Conclusion Hypoxia can induce SHG44 cells to form VM.VEGF-EphA2-MMPs-VM may be the key pathway for VM formation.

关 键 词：缺氧 星形细胞瘤 SHG44细胞 血管生成拟态 机制 

分 类 号：R739.41[医药卫生—肿瘤]