Hu Wen-Hao, Hu Zhe, Shen Xian, Dong Li-Yang, Zhou Wei-Zhong, Yu Xi-Xiang
Department of Interventional Radiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejing, China.
Department of Interventional Radiology, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, China.
Exp Mol Pathol. 2016 Feb;100(1):101-8. doi: 10.1016/j.yexmp.2015.10.001. Epub 2015 Oct 22.
C5a and its receptor, C5a receptor (C5aR), play critical roles in tumor progression. However, mechanisms of C5a-C5aR axis in hepatocellular carcinoma (HCC) cell invasiveness are not fully elucidated. In this study, we found that C5aR expression was highly expressed in HCC cell lines and tumor tissues, and associated with capsular invasion, tumor stage and some epithelial-mesenchymal transition (EMT)-related markers. Activation of C5aR by C5a promoted HCC cell invasion and migration, whereas depletion of C5aR expression significantly impaired C5a-stimulated invasion and migration. Furthermore, we found that C5aR induced EMT in HCC cells, through downregulation of E-cadherin and Claudin-1 expression, and upregulation of Snail expression. Finally, we demonstrated that C5aR stimulated activation of ERK1/2, and ERK1/2 pathway was involved in C5aR-mediated EMT, cell invasion and migration of HCC cells. Thus, our data suggest that C5aR stimulates cell invasion and migration via ERK1/2-mediated EMT in HCC cells, and implicate that blocking C5aR expression has therapeutic promise to inhibit HCC invasiveness.
C5a及其受体C5a受体（C5aR）在肿瘤进展中发挥关键作用。然而，C5a-C5aR轴在肝细胞癌（HCC）细胞侵袭中的机制尚未完全阐明。在本研究中，我们发现C5aR在HCC细胞系和肿瘤组织中高表达，并与包膜侵犯、肿瘤分期以及一些上皮-间质转化（EMT）相关标志物有关。C5a激活C5aR可促进HCC细胞侵袭和迁移，而C5aR表达的缺失则显著削弱C5a刺激的侵袭和迁移。此外，我们发现C5aR通过下调E-钙黏蛋白和Claudin-1的表达以及上调Snail的表达诱导HCC细胞发生EMT。最后，我们证明C5aR刺激ERK1/2的激活，并且ERK1/2通路参与C5aR介导的EMT、HCC细胞的侵袭和迁移。因此，我们的数据表明C5aR通过ERK1/2介导的EMT刺激HCC细胞的侵袭和迁移，并提示阻断C5aR表达对抑制HCC侵袭具有治疗前景。
