ANGPTL2 promotes tumor metastasis in hepatocellular carcinoma
ANGPTL2 promotes tumor metastasis in hepatocellular carcinoma
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ANGPTL2促进肝细胞癌的肿瘤转移
DOI：
10.1111/jgh.12702
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发表时间：
2015-02-01
影响因子：
4.1
通讯作者：
Li, Hong
中科院分区：
文献类型：
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作者：
Gao, Lin;Ge, Chao;Li, Hong
背景与目的血管生成素样蛋白2（Angiopoietin-like protein 2，ANGPTL 2）在代谢、血管生物学、炎症和肿瘤转移中发挥着多种作用，但其在人肝细胞癌（hepatocellular carcinoma，HCC）转移中的作用尚不清楚。本研究旨在进一步探讨ANGPTL 2在肝癌细胞迁移和侵袭中的作用。方法采用实时定量PCR、Western blotting、免疫组化、transwell迁移和侵袭实验等方法，研究ANGPTL 2在肝癌细胞迁移和侵袭中的作用。ANGPTL 2在HCC组织中的表达高于匹配的非癌肝组织。HCC组织中ANGPTL 2水平与HCC患者肝内转移呈正相关。ANGPTL 2过表达可显著增加肝癌细胞的体外迁移和侵袭能力，促进肝癌细胞的肝内和肺远端转移，而内源性ANGPTL 2敲低可降低肝癌细胞的体外迁移和侵袭能力。集落形成实验和3-（4，5-Dimethylthiazol-2-yl）-2，5-diphenyltetrazolium bromide（MTT）实验显示ANGPTL 2在体外不影响细胞增殖，而ANGPTL 2的过表达促进了异种移植动物模型中的肿瘤形成。
Background and AimAngiopoietin-like protein 2 (ANGPTL2) plays various roles in metabolism, vascular biology, inflammation, and tumor metastasis, but little is known about its function in human hepatocellular carcinoma (HCC) metastasis. This study aimed to further explore the function of ANGPTL2 on migration and invasion of liver cancer cells.MethodsQuantitative real-time polymerase chain reaction, Western blotting, immunohistochemistry, transwell migration, and invasion assays were performed to clarify the function of ANGPTL2 in the regulation of cell migration and invasion in human HCC.ResultsIn HCC patients, ANGPTL2 expression was higher in HCC tissues compared with matched noncancerous liver tissues. And the ANGPTL2 levels of HCC tissues positively correlated with intrahepatic metastasis in HCC patients. Overexpression of ANGPTL2 significantly increased migration and invasion of HCC cells in vitro, and promoted intrahepatic and distal pulmonary metastasis in vivo, while knockdown of endogenous ANGPTL2 resulted in a reduced migration and invasion in vitro. Colony formation assay and 3-(4,5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay showed ANGPTL2 did not affect cell proliferation in vitro, whereas overexpression of ANGPTL2 promoted tumor formation in xenograft animal model.ConclusionsOur findings show that ANGPTL2 drives human HCC metastasis and provides a potential therapeutic target for HCC treatment.