B7-H3 promotes aggression and invasion of hepatocellular carcinoma by targeting epithelial-to-mesenchymal transition via JAK2/STAT3/Slug signaling pathway.
B7-H3 promotes aggression and invasion of hepatocellular carcinoma by targeting epithelial-to-mesenchymal transition via JAK2/STAT3/Slug signaling pathway.
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DOI：
10.1186/s12935-015-0195-z
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发表时间：
2015
影响因子：
5.8
通讯作者：
Sun DX
中科院分区：
文献类型：
--
作者：
Kang FB;Wang L;Jia HC;Li D;Li HJ;Zhang YG;Sun DX
B7同源蛋白3（B7-H3）是一种新近发现的免疫调节蛋白，在人肝细胞癌（HCC）组织中高表达。然而，B7-H3的动态表达模式是否有助于HCC的早期侵袭在很大程度上是未知的。此外，B7-H3在HCC中的生物学作用仍不清楚。在此，我们将检测B7-H3在原发性和转移性HCC中的表达谱及其临床病理学意义，并进一步确定B7-H3敲低是否模拟HCC进展和转移的不同病理状态。采用免疫组化方法，研究了116例原发性和转移性肝癌中B7-H3的表达。生存曲线和对数秩检验用于检验B7-H3表达与生存的关联。利用RNA干扰技术建立B7-H3缺失的肝癌细胞系，研究B7-H3对肝癌细胞增殖、凋亡、迁移和侵袭能力的影响。临床病例统计分析显示，B7-H3高表达组倾向于TNM分期晚期，存在血管浸润、淋巴结转移和微卫星肿瘤形成。在转移性HCC肿瘤中检测到肿瘤B7-H3染色强度的增加更显著。体外实验结果表明，B7-H3能够通过JAK 2/Stat 3/Slug信号通路靶向上皮间质转化（EMT），促进肝癌细胞的创伤愈合、转移和侵袭，而对细胞生长和凋亡无明显影响。B7-H3对肝癌细胞转移能力的调节使其成为抗转移治疗的一个有希望的靶点。本文的在线版本（doi：10.1186/s12935-015-0195-z）包含补充材料，可供授权用户使用。
B7-homologue 3 (B7-H3), a recently identified immunoregulatory protein, has been shown to be overexpressed in human hepatocellular carcinoma (HCC). However, whether the dynamic expression pattern of B7-H3 contributes to early invasion of HCC is largely unknown. In addition, the biological roles of B7-H3 in HCC are still unclear. Herein, we are going to examine B7-H3 expression profile and its clinicopathological significance in primary and metastatic HCC, and further determine whether B7-H3 knockdown simulates different pathological states of HCC progression and metastasis. Using immunohistochemistry, B7-H3 expression was studied on 116 HCC containing primary and metastatic HCCs. Survival curves and log-rank tests were used to test the association of B7-H3 expression with survival. HCC cells with B7-H3 depletion were established by RNA interference to investigate the effect of B7-H3 on cell proliferation, apoptosis, migration and invasion in vitro. Statistical analysis of clinical cases revealed that B7-H3 high expression group had inclinations towards late TNM stage, the presence of vascular invasion, lymph metastasis, and the formation of microsatellite tumors. Increased intensity of tumor B7-H3 staining was detected more significantly in metastatic HCC tumors. Consistently in experiments performed in vitro, B7-H3 was able to stimulate the wound healing, metastasis and invasion of hepatoma cells by targeting epithelial-to-mesenchymal transition (EMT) via JAK2/Stat3/Slug signaling pathway, while no obvious influence on cell growth and apoptosis. B7-H3 in the regulation of the metastatic capacity of HCC cells makes itself a promising therapeutic target for anti-metastasis therapy. The online version of this article (doi:10.1186/s12935-015-0195-z) contains supplementary material, which is available to authorized users.
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影响因子：
11.2
作者：
Barkan D;Kleinman H;Simmons JL;Asmussen H;Kamaraju AK;Hoenorhoff MJ;Liu ZY;Costes SV;Cho EH;Lockett S;Khanna C;Chambers AF;Green JE
通讯作者：
Green JE
影响因子：
3.7
作者：
Wang L;Zhang Q;Chen W;Shan B;Ding Y;Zhang G;Cao N;Liu L;Zhang Y
通讯作者：
Zhang Y
影响因子：
5.7
作者：
Liu H;Tekle C;Chen YW;Kristian A;Zhao Y;Zhou M;Liu Z;Ding Y;Wang B;Mælandsmo GM;Nesland JM;Fodstad O;Tan M
通讯作者：
Tan M
影响因子：
4.4
作者：
Luo, LQ;Chapoval, AI;Chen, LP
通讯作者：
Chen, LP
影响因子：
4.1
作者：
Wang, Hongyang;Chen, Lei
通讯作者：
Chen, Lei