肿瘤细胞微环境对胶质瘤血管生成拟态形成的影响

Influence of tumor microenvironment on vasculogenic mimicry formation in glioma

目的探讨肿瘤细胞微环境改变对胶质瘤血管生成拟态(VM)形成的影响。方法通过制造化学缺氧环境、添加U251上清和用U251细胞预处理Matrigel等3种方法诱导胶质瘤细胞SHG44形成VM,并检测上述几种培养基上清中的血管内皮生长因子(VEGF)、转化生长因子-β(TGF-β)、成纤维细胞生长因子(b FGF)、血小板源生长因子(PDGF)及肿瘤坏死因子-α(TNF-α)的表达与对照组SHG44细胞的差异,同时比较组间基质金属蛋白酶(MMP)活性水平。结果几种方法均能诱导SHG44细胞形成VM结构,其中缺氧组VM形成能力最强,添加U251上清组次之,U251细胞预处理Matrigel组最弱,且几个处理组上清中的VEGF、TGF-β和PDGF浓度与各组VM形成能力相关,MMP-2活性也与VM形成能力相关。结论胶质瘤VM形成很可能是微环境改变后多种因素作用的结果,其中VEGF、TGF-β、PDGF、MMP-2与VM形成关系具有相关性。

Objective To study the influence of tumor microenvironment on vasculogenic mimicry（VM） formation in glioma. Methods We induced VM formation in glioma cell line SHG44 by three ways, including creating a chemical hypoxic environment, adding U251 cell culture supernatant and preteating Matrigel with U251. Then, we detected the expression of VEGF, TGF-β, b FGF, PDGF and TNF-α in the supernatant of each culture. The MMP activities were also tested. Results VM network formed by SHG44 was successfully induced in all the groups. The capability of VM formation was different among the three groups, with the best result seen in the hypoxic group. In the other two groups, the group with U251 supernatant was better than the Matrigel pretreatment by U251 group. Expression of VEGF, TGF-β and PDGF in each group were correlated with capability of VM formation. MMP-2 activity was also correlated with capability of VM formation. Conclusion VM formed by glioma cells might be induced by multi-factor in the hypoxic tumor microenvironment. Expression of VEGF, TGF-β, PDGF and MMP-2 were correlated with VM formation in glioma.