Gao Lin, Ge Chao, Fang Tao, Zhao Fangyu, Chen Taoyang, Yao Ming, Li Jinjun, Li Hong
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
J Gastroenterol Hepatol. 2015 Feb;30(2):396-404. doi: 10.1111/jgh.12702.
Angiopoietin-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.
Quantitative 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.
In 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.
Our findings show that ANGPTL2 drives human HCC metastasis and provides a potential therapeutic target for HCC treatment.
血管生成素样蛋白2(ANGPTL2)在代谢、血管生物学、炎症及肿瘤转移中发挥多种作用,但对其在人类肝细胞癌(HCC)转移中的功能了解甚少。本研究旨在进一步探讨ANGPTL2对肝癌细胞迁移和侵袭的作用。
采用定量实时聚合酶链反应、蛋白质免疫印迹法、免疫组织化学、Transwell迁移和侵袭实验,以阐明ANGPTL2在调控人类HCC细胞迁移和侵袭中的作用。
在HCC患者中,与配对的癌旁肝组织相比,ANGPTL2在HCC组织中的表达更高。且HCC组织中ANGPTL2水平与HCC患者肝内转移呈正相关。ANGPTL2的过表达显著增加了HCC细胞的体外迁移和侵袭能力,并促进了体内肝内及远处肺转移,而敲低内源性ANGPTL2则导致体外迁移和侵袭能力降低。集落形成实验和3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐(MTT)实验表明,ANGPTL2在体外不影响细胞增殖,而ANGPTL2的过表达在异种移植动物模型中促进肿瘤形成。
我们的研究结果表明,ANGPTL2驱动人类HCC转移,并为HCC治疗提供了一个潜在的治疗靶点。