The role of TMPRSS4 in radiation induced metastasis of hepatocellular carcinoma / 中华肝胆外科杂志

ABSTRACT

Objective To investigate the role and mechanism of TMPRSS4 in radiation induced metastasis of hepatocellular carcinoma (HCC).Methods Metastatic model of human HCC was established by orthotopic implantation of histologically intact human HCC tissue into the liver of nude mice.Mice bearing xenografts in liver were killed after radiation and the residual tumors were resected and reimplanted into the liver of normal nude mice.At the end of sixth week,the mice were killed and the histopathological features,tumor volume,intrahepatic and lung metastasis were evaluated.Expression of epithelial-mesenchymal transition (EMT) related genes including N-cadherin,Vimentin,SIP1 and TMPRSS4 were measured by Western blotting and RT-PCR.Results The tumor volume and frequency of lung metastasis of control group was 2.25±0.52 cm3 and 66.7％,respectively.Compared to control group,tumor diameter (1.61±0.51 cm3,P＜0.05) and lung metastasis (12.5％,P＜0.05) were significantly inhibited 2 days after radiation.Whereas,30 days after radiation,tumor growth recovered (2.60±0.61 cm3,P＞0.05) and lung metastasis was enhanced (100％,P＜0.05).There were no intrahepatic metastasis in the control group and in the group of reimplantation of HCC 2 days after radiation,while the tumors from those 30 days after radiation showed enhanced intrahepatic metastasis (18 ± 8.05,P＜ 0.01 ),with overexpression of SIP1,N-cadherin,Vimentin and TMPRSS4,and reduced expression of E-cadherin.Conclusion The metastasis potential of residual HCC after radiation was first inhibited and then promoted.Overexpression of TMPRSS4 plays a critical role in radiation induced long-term metastasis of HCC by facilitating EMT.