CD276 Promotes Vasculogenic Mimicry Formation in Hepatocellular Carcinoma via the PI3K/AKT/MMPs Pathway.
CD276 Promotes Vasculogenic Mimicry Formation in Hepatocellular Carcinoma via the PI3K/AKT/MMPs Pathway.
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DOI：
10.2147/ott.s271891
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发表时间：
2020
影响因子：
4
通讯作者：
Chen YL
中科院分区：
文献类型：
--
作者：
Cheng R;Wang B;Cai XR;Chen ZS;Du Q;Zhou LY;Ye JM;Chen YL
CD 276蛋白表达和血管生成拟态（VM）形成与肝细胞癌（HCC）患者的不良预后相关。虽然CD 276和VM形成的作用都涉及基质金属蛋白酶的激活，但它们之间的关系尚未被探索。以下研究探讨了CD 276表达对VM形成的影响及其潜在机制。应用免疫组化和CD 31/PAS双染色技术检测商品化组织芯片中CD 276表达和VM。用抗CD 276的shRNA慢病毒载体转染肝癌细胞系，观察肿瘤细胞的增殖、侵袭、迁移和管状结构的形成。Western blot、免疫荧光和明胶酶谱法检测MMP 14、MMP 2、VE-钙粘蛋白、E-钙粘蛋白和波形蛋白的表达及MMP活化情况。此外，在体内建立了HCC细胞的原位异种移植模型，之后检测VM及其标记分子沿着。CD 276表达与肝癌患者VM和预后不良有关。RNA干扰CD 276在体外和体内降低肿瘤细胞增殖、侵袭、迁移和VM形成。CD 276基因敲低可上调E-cadherin的表达，抑制AKT的磷酸化，抑制MMP 14、MMP 2、VE-cadherin、vimentin的表达，抑制MMP 2和MMP 9的活化。CD 276可能通过激活PI 3 K/AKT/MMPs信号通路，诱导HCC发生EMT，从而促进VM的形成。CD 276有可能成为抗VM治疗HCC的一个有希望的候选者。
CD276 protein expression and vasculogenic mimicry (VM) formation are associated with the poor prognosis of hepatocellular carcinoma (HCC) patients. Although both the effects of CD276 and VM formation involve the activation of matrix metalloproteinases, and their relationship has not yet been explored. The following study investigated the effect of CD276 expression on VM formation and the potential mechanisms. CD276 expression and VM were examined in commercial tissue microarrays by immunohistochemistry and CD31/PAS double staining. Tumor cell proliferation, invasion, migration and, tube formation were detected in vitro after transfecting HCC cell lines with an shRNA lentiviral vector against CD276. The expression of MMP14, MMP2, VE-cadherin, E-cadherin, and vimentin and MMPs activation was detected by Western blot, immunofluorescence and gelatin zymography assay. In addition, an orthotopic xenograft model of HCC cells was established in vivo, after which VM was detected, along with its marker molecules. CD276 expression was associated with VM and poor prognosis in HCC patients. RNA interference of CD276 reduced tumor cell proliferation, invasion, migration, and VM formation in vitro and in vivo. Furthermore, CD276 knockdown up-regulated the expression of E-cadherin but inhibited the phosphorylation of AKT, the expression of MMP14, MMP2, VE-cadherin, vimentin and the activation of MMP2 and MMP9 in HCC cell lines. CD276 may promote VM formation by activating the PI3K/AKT/MMPs pathway and inducing the EMT process in HCC. CD276 may serve as a promising candidate for the anti-VM treatment of HCC.