Activated hepatic stellate cells promote hepatocellular carcinoma cell migration and invasion via the activation of FAK-MMP9 signaling
Activated hepatic stellate cells promote hepatocellular carcinoma cell migration and invasion via the activation of FAK-MMP9 signaling
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激活的肝星状细胞通过激活FAK-MMP9信号促进肝细胞癌细胞迁移和侵袭
DOI：
10.3892/or.2013.2872
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发表时间：
2014-02-01
期刊：
影响因子：
4.2
通讯作者：
Liu, Qingguang
中科院分区：
文献类型：
--
作者：
Han, Shaoshan;Han, Lei;Liu, Qingguang
活化的肝星状细胞（hepatic stellate cells，HSCs）是肝肿瘤微环境中的主要基质细胞，可促进肝癌细胞的生长和迁移。然而，激活的HSC发挥其致癌作用的潜在机制至今尚未完全了解。在本研究中，我们研究了活化的HSC数量及其在HCC中的临床病理意义，并揭示了其与粘着斑激酶（FAK）-MMP 9信号转导的相关性。肝星状细胞的活化与肿瘤侵犯门静脉、TNM分期及肿瘤分化程度有关。HCC中活化的HSC数量与p-FAK和MMP 9的表达水平呈正相关。此外，我们还研究了活化的HSC对肝癌细胞体外迁移和侵袭的影响。条件培养基（CM）从活化的HSC或与活化的HSC共培养显着诱导肝癌细胞的迁移和侵袭。此外，在活化的HSC-CM和共培养物的存在下证实了HCC中FAK-MMP 9信号传导的活化。用FAK短发夹RNA（shRNA）抑制HCC细胞中FAK-MMP 9信号传导可消除活化的HSC对HCC细胞的作用。总之，我们的数据表明，在肿瘤微环境中激活的HSC通过激活FAK-MMP 9信号传导促进HCC细胞迁移和侵袭。
Activated hepatic stellate cells (HSCs) are the major subtype of stromal cells in the liver tumor microenvironment which can promote the growth and migration of hepatocellular carcinoma (HCC) cells. However, the underlying mechanisms by which activated HSCs exert their oncogenic effects are not fully understood to date. In the present study, we investigated the number of activated HSCs and its clinicopathological significance in HCC and uncovered its correlation with focal adhesion kinase (FAK)-MMP9 signaling. A higher number of activated HSCs was associated with tumor invasion of the portal vein, advanced TNM stage and poorer tumor differentiation. The number of activated HSCs was positively correlated with the expression levels of p-FAK and MMP9 in HCC. Furthermore, we studied the effects of activated HSCs on the migration and invasion of HCC cells in vitro. Conditioned medium (CM) from activated HSCs or co-culture with activated HSCs significantly induced the migration and invasion of HCC cells. In addition, activation of FAK-MMP9 signaling in HCC was demonstrated in the presence of activated HSC-CM and of co-culture. Inhibition of FAK-MMP9 signaling in HCC cells with FAK short hairpin RNA (shRNA) abrogated the effects of activated HSCs on HCC cells. Taken together, our data suggest that activated HSCs in the tumor microenvironment promote HCC cell migration and invasion via activation of FAK-MMP9 signaling.