Qiu Wei, Wang Guangyi, Sun Xiaodong, Ye Junfeng, Wei Feng, Shi Xiaoju, Lv Guoyue
Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Jilin University, 71 Xinmin Street, Changchun, 130021, Jilin, China.
Med Oncol. 2015 Mar;32(3):75. doi: 10.1007/s12032-015-0530-1. Epub 2015 Feb 20.
In recent years, the chemokine CC receptor 6 (CCR6) and its ligand CCL20 were reported to play an essential role in hepatocellular carcinoma (HCC). However, the role of cell surface nucleolin in the CCR6 pathway of HCC is not well featured. Using immunohistochemistry, Western blotting, siRNA, wound healing and transwell assay, we investigated the relationships of cell surface nucleolin and CCR6 signaling in HCC. In the present study, our findings identified that cell surface nucleolin and CCR6 protein were stained in most of HCC tissues (64, 68 %, respectively) and differently expressed in HCC cell lines; meanwhile, both expression has an association with advanced stage, lymph node metastasis and poor 5-year prognosis. According to in vitro assays, we found that the silencing of either cell surface nucleolin or CCR6 inhibited the protein expression of p-ERK, p-AKT, MMP2, MMP9 and ICAM-1 in the CCL20-stimulated HCCLM6 cells. Functional analysis revealed that cell surface nucleolin or CCR6 silencing significantly hampered HCCLM6 cell motility and invasiveness ability, when compared with control. In conclusion, this work suggests that cell surface nucleolin participates in the initiation of CCR6 pathway and biological behaviors of HCC, leading to HCC cell adhesion, migration and invasive behavior. In the clinical practice, cell surface nucleolin and CCR6 are recommended to predict poor prognosis and be used as a useful target for HCC patients.
近年来，据报道趋化因子CC受体6（CCR6）及其配体CCL20在肝细胞癌（HCC）中发挥重要作用。然而，细胞表面核仁素在HCC的CCR6通路中的作用尚未得到充分阐明。我们使用免疫组织化学、蛋白质印迹、小干扰RNA、伤口愈合实验和Transwell实验，研究了细胞表面核仁素与HCC中CCR6信号传导之间的关系。在本研究中，我们的研究结果表明，大多数HCC组织中细胞表面核仁素和CCR6蛋白均有染色（分别为64%和68%），且在HCC细胞系中表达不同；同时，二者的表达均与晚期、淋巴结转移及5年预后不良相关。根据体外实验，我们发现沉默细胞表面核仁素或CCR6均可抑制CCL20刺激的HCCLM6细胞中p-ERK、p-AKT、MMP2、MMP9和ICAM-1的蛋白表达。功能分析显示，与对照组相比，细胞表面核仁素或CCR6沉默显著阻碍了HCCLM6细胞的运动性和侵袭能力。总之，本研究表明细胞表面核仁素参与了CCR6通路的启动及HCC的生物学行为，导致HCC细胞发生黏附、迁移和侵袭行为。在临床实践中，建议将细胞表面核仁素和CCR6作为预测预后不良的指标，并作为HCC患者的有效治疗靶点。
