BMP4 通过诱导EMT 促进肝癌迁移侵袭*

目的:检测BMP 4 在肝癌中的表达并探讨BMP 4 在诱导肝癌EMT 中的作用，进而研究其对肝癌细胞迁移侵袭能力的影响。方法:采用免疫组织化学方法检测肝癌组织中BMP 4 的表达，分析其与肝癌临床病理资料之间的关系。将BMP 4 表达质粒转染至肝癌细胞系HepG2 中，诱导BMP 4 外源性过表达。观察BMP 4 转染前、后HepG2 的细胞形态学改变；Westernblot检测转染前、后HepG2 中BMP 4、EMT 相关蛋白（E-cadherin、Vimentin）表达变化情况；划痕和侵袭实验检测BMP 4 对细胞迁移侵袭能力的影响。结果:BMP 4 与患者的年龄、病理分级、临床分期、不良预后密切相关。BMP 4 过表达后HepG2 呈现典型的EMT 形态学改变，E-cadherin 表达下调、Vimentin 表达上调、细胞的迁移侵袭能力显著增强。结论:BMP 4 与肝癌临床病理资料密切相关，并可能通过诱导EMT 促进肝癌细胞的迁移侵袭能力。 

BMP4 promotes migration and invasion of hepatocellular carcinoma by inducing epithelial-mesenchymal transition

Objective:To determine the expression of BMP4 in hepatocellular carcinoma (HCC) and to study the role of BMP 4 in inducing epithelial-mesenchymal transition (EMT) to analyze the effect of BMP 4 on the migration and invasion of HCC cells. Methods:The expression of BMP 4 in HCC specimens was examined by immunohistochemistry staining, and the correlations were analyzed between the expression of BMP4 and clinicopathological data. The BMP4 expression plasmid was transfected into HepG2 cells to induce exogenous overexpression of BMP4 protein. The changes of HepG 2 cell morphology were detected after BMP 4 transfection by using a microscope; the changes of the expression of BMP4, EMT-related protein (E-cadherin, Vimentin) in HepG 2 cells were detected by Western blot after transfection of BMP 4; the wound healing assay in vitro was used to detect the effects of BMP4 gene transfection on the ability of migration of HepG 2 cells; the invasion assay was used to determine the role of transfection of BMP 4 on the invasive potential of HepG 2 cells. Results: Immunohistochemistry staining method displayed that BMP4 expression was positively associated with age, histological differentiation, stage, and poor prognosis. After BMP 4 overexpression, the morphology of HepG2 cells showed significant changes from a paving stone structure with cell-cell adhesion to a fibroblastic shape, which showed typical EMT change; Western blot exhibited that the expression of E-cadherin was downregulated and the Vimentin expression was upregulated in HepG 2 cells; the wound healing and invasion assay showed that the migration and invasion potentials of HepG 2 cells were significantly enhanced. Conclusion:BMP4, which displayed a high expression in HCC specimens, was closely associated with clinicopathologic data, and BMP4 may promote migration and invasion of HCC cells by inducing epithelial-mesenchymal transition.