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MIG7调节肝细胞癌中血管生成拟态的形成及其对肝癌转移潜能的影响

MIG7 Regulates the Vasculogenic Mimicry Formation in Hepatocellular Carcinoma then Effects the Metastasis

  • 摘要: 目的探讨肝细胞癌(HCC)中迁移诱导基因7( MIG7)的表达与血管生成拟态(VM)形成的相关性,以及MIG7的表达与不同肝癌细胞株VM形成能力及转移潜能的关系。方法应用免疫组织化学方法分析配对的40例HCC原发灶及其转移灶标本中MIG7蛋白的表达和VM形成情况;应用三维培养技术培养不同转移潜能的人肝癌细胞株(高转移潜能肝癌细胞MHCC-97H、低转移潜能肝癌细胞MHCC-97L和非转移肝癌细胞Huh-7)及人正常肝细胞L-02,分别检测VM形成情况; 应用RT-PCR技术检测不同转移潜能肝癌细胞中 MIG7 mRNA的水平;应用Western blot技术检测不同转移潜能肝癌细胞株中MIG7蛋白表达水平。结果①40例配对的HCC原发灶和相应转移灶中,MIG7蛋白的表达与VM形成呈正相关( rs=0.595,PMIG7 mRNA和蛋白表达及VM的形成能力均大于低转移潜能肝癌细胞株MHCC-97L及非转移肝癌细胞株Huh-7。人正常肝细胞L-02未见VM形成。结论MIG7高表达的肝癌组织中VM形成能力强,MIG7通过调节VM的形成影响HCC的侵袭转移,MIG7是抑制HCC侵袭转移的潜在靶点。

     

    Abstract: Objective To investigate the expression of migration-inducing gene 7 (MIG7) in different HCC lines and its relationship with vasculogenic mimicry (VM) formation and metastatic potentiality. Methods Employing immunostaining to detect MIG7 protein expression and VM formation in 40 matched pairs of primary and metastatic HCC specimens from 40 patients, and investigating the correlation of VM formation with MIG7 protein expression. Detecting VM formation in HCC lines with different metastatic ability (MHCC-97H, MHCC-97L, Huh-7) and human normal hepatocyte line (L-02) through three-dimensional culture, and detecting MIG7 mRNA expression with RT-PCR, investigating the correlation of MIG7 protein expression with VM formation and HCC metastatic potentiality with Western blot assay; screening the HCC cell line with high MIG7 expression. Results In 40 matched pairs of HCC tissue, there was a significant positive correlation between MIG7 protein expression and VM formation ( rs=0.595, P<0.01). The capability of VM formation of MHCC-97H with high metastatic potentiality was stronger than that of MHCC-97L with low metastatic potentiality and Huh-7 with non-metastatic potentiality, and there was no VM formation in L-02. The result of RT-PCR and Western blot assay indicated the same. Conclusion MIG7 expression in HCC tissue is high and correlated positively with VM formation. MIG7 expression in different HCC cell lines is coincident with theirs VM formation, invasion and metastasis. MIG7 is a potential target for inhibiting the invasion and metastasis of HCC.

     

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