Overexpression of a disintegrin and metalloproteinase 21 is associated with motility, metastasis, and poor prognosis in hepatocellular carcinoma.
Overexpression of a disintegrin and metalloproteinase 21 is associated with motility, metastasis, and poor prognosis in hepatocellular carcinoma.
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DOI：
10.1038/s41598-017-15800-z
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发表时间：
2017-11-14
影响因子：
4.6
通讯作者：
Terai S
中科院分区：
文献类型：
--
作者：
Honda H;Takamura M;Yamagiwa S;Genda T;Horigome R;Kimura N;Setsu T;Tominaga K;Kamimura H;Matsuda Y;Wakai T;Aoyagi Y;Terai S
细胞运动在肝细胞癌（HCC）肝内转移中起重要作用，并预示患者预后不良。本研究调查了去整合素和金属蛋白酶（亚当斯）在HCC中的作用，因为这些蛋白质已知与细胞运动相关。本研究证实了12个具有金属蛋白酶活性的亚当斯在肝癌细胞中的表达，并建立了稳定表达针对ADAM 21的短干扰RNA的KYN-2肝癌细胞系，以研究ADAM 21缺陷对肝癌细胞运动和转移的影响。我们还通过免疫组化检测了119例HCC患者队列中的ADAM 21表达。ADAM 21在KYN-2细胞中过表达，相对于对照，其敲低降低了侵袭、迁移、增殖和转移。在临床标本中，与ADAM 21表达阴性的病例相比，ADAM 21阳性与血管浸润、大肿瘤大小、高组织学分级以及较低的总体和无复发生存率相关。多变量分析显示，ADAM 21阳性是总体（P = 0.003）和无复发（P = 0.001）生存的独立危险因素。这些结果表明，ADAM 21在HCC转移中起作用，并可作为疾病进展的预后标志物。
Cell motility plays an important role in intrahepatic metastasis of hepatocellular carcinoma (HCC), and predicts poor prognosis in patients. The present study investigated the role of a disintegrin and metalloproteinases (ADAMs) in HCC, since these proteins are known to be associated with cell motility. We confirmed the expression of 12 ADAMs with putative metalloproteinase activity in HCC cells, and established a KYN-2 HCC cell line stably expressing short interfering RNA against ADAM21 to investigate the effect of ADAM21 deficiency on HCC cell motility and metastasis in vitro and in vivo. We also examined ADAM21 expression in a cohort of 119 HCC patients by immunohistochemistry. ADAM21 was overexpressed in KYN-2 cells, and its knockdown reduced invasion, migration, proliferation, and metastasis relative to controls. In clinical specimens, ADAM21 positivity was associated with vascular invasion, large tumor size, high histological grade, and lower overall and recurrence-free survival as compared to cases that were negative for ADAM21 expression. A multivariate analysis revealed that ADAM21 positivity was an independent risk factor for overall (P = 0.003) and recurrence-free (P = 0.001) survival. These results suggest that ADAM21 plays a role in HCC metastasis and can serve as a prognostic marker for disease progression.
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影响因子：
158.5
作者：
Llovet, Josep M.;Ricci, Sergio;Bruix, Jordi
通讯作者：
Bruix, Jordi
影响因子：
4.8
作者：
Chan, Michael;Huang, Yi-Wen;Lin, Huey-Jen L.
通讯作者：
Lin, Huey-Jen L.
DOI：
10.1016/j.bbrc.2014.11.093
发表时间：
2015-01-02
影响因子：
3.1
作者：
Shan, Nianxi;Shen, Liangfang;Duan, Chaojun
通讯作者：
Duan, Chaojun
影响因子：
64.8
作者：
Fischer KR;Durrans A;Lee S;Sheng J;Li F;Wong ST;Choi H;El Rayes T;Ryu S;Troeger J;Schwabe RF;Vahdat LT;Altorki NK;Mittal V;Gao D
通讯作者：
Gao D
影响因子：
13.5
作者：
Genda, T;Sakamoto, M;Hirohashi, S
通讯作者：
Hirohashi, S