趋化因子配体20通过上皮-间质转化促进肝细胞癌进展。
Chemokine ligand 20 enhances progression of hepatocellular carcinoma via epithelial-mesenchymal transition.
作者信息
Hou Ke-Zhu, Fu Zhi-Qiang, Gong Hua
机构信息
Ke-Zhu Hou, Zhi-Qiang Fu, Hua Gong, Department of First General Surgery, Shidong Hospital, Shanghai 200438, China.
出版信息
World J Gastroenterol. 2015 Jan 14;21(2):475-83. doi: 10.3748/wjg.v21.i2.475.
AIM
To identify the mechanisms of chemokine ligand 20 (CCL20)-induced hepatocellular carcinoma (HCC) metastasis and evaluate it as a prognostic marker.
METHODS
Expression of CCL20 was evaluated by immunohistochemistry in HCC tissues from 62 patients who underwent curative resection. The relationship between CCL20 expression and clinicopathologic features was analyzed. Univariate and multivariate analyses were performed to evaluate its predictive value for recurrence and survival of HCC patients. The expression levels of epithelial-mesenchymal transition (EMT)-and signaling pathway-related proteins were evaluated by Western blotting and immunocytochemistry. The effects of CCL20 on HCC cell proliferation and migration were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenoltetrazolium bromide (MTT) and Transwell assays.
RESULTS
CCL20 immunoreactivity was detected in all 62 patient specimens. CCL20 expression was associated with preoperative alpha-fetoprotein level (P = 0.043), tumor size (P = 0.000), tumor number (P = 0.008), vascular invasion (P = 0.014), and tumor differentiation (P = 0.007). Patients with high CCL20 expression had poorer recurrence-free and overall survivals compared to those with low CCL20 expression (both P < 0.001). CCL20 induced EMT-like changes in HCC cells and increased their proliferation and migration ability (P < 0.05). Western blotting and immunofluorescence staining showed that CCL20 induced an EMT-like phenotype in HCC cells, and increased expression of phosphorylated AKT, β-catenin and vimentin, and decreased E-cadherin expression (P < 0.05). The correlation analysis revealed that high CCL20 expression in HCC tissue specimens was negatively correlated with E-cadherin expression (13.33%, 4/30), and positively correlated with vimentin (90.0%, 27/30), β-catenin (96.67%, 29/30) and p-AKT (76.67%, 23/30) expression.
CONCLUSION
CCL20 expression is associated with HCC recurrence and patient survival and promotes HCC cell proliferation and migration by inducing EMT-like changes via PI3K/AKT and Wnt/β-catenin pathways.
目的
确定趋化因子配体20（CCL20）诱导肝细胞癌（HCC）转移的机制，并评估其作为预后标志物的价值。
方法
采用免疫组织化学法评估62例行根治性切除的HCC患者组织中CCL20的表达。分析CCL20表达与临床病理特征之间的关系。进行单因素和多因素分析以评估其对HCC患者复发和生存的预测价值。通过蛋白质印迹法和免疫细胞化学法评估上皮-间质转化（EMT）及信号通路相关蛋白的表达水平。采用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）法和Transwell实验分析CCL20对HCC细胞增殖和迁移的影响。
结果
在所有62例患者标本中均检测到CCL20免疫反应性。CCL20表达与术前甲胎蛋白水平（P = 0.043）、肿瘤大小（P = 0.000）、肿瘤数量（P = 0.008）、血管侵犯（P = 0.014）及肿瘤分化程度（P = 0.007）相关。与CCL20低表达患者相比，CCL20高表达患者的无复发生存期和总生存期更差（均P < 0.001）。CCL20诱导HCC细胞发生EMT样改变，并增强其增殖和迁移能力（P < 0.05）。蛋白质印迹法和免疫荧光染色显示，CCL20诱导HCC细胞出现EMT样表型，增加磷酸化AKT、β-连环蛋白和波形蛋白的表达，并降低E-钙黏蛋白的表达（P < 0.05）。相关性分析显示，HCC组织标本中CCL20高表达与E-钙黏蛋白表达呈负相关（13.33%，4/30），与波形蛋白（90.0%，27/30）、β-连环蛋白（96.67%，29/30）和p-AKT（76.67%，23/30）表达呈正相关。
结论
CCL20表达与HCC复发及患者生存相关，并通过PI3K/AKT和Wnt/β-连环蛋白通路诱导EMT样改变，促进HCC细胞增殖和迁移。
Zotero 插件