TMPRSS4 promotes invasiveness of human gastric cancer cells through activation of NF-κB/MMP-9 signaling.

Transmembrane protease serine 4 (TMPRSS4) is a type-II transmembrane serine protease that is frequently upregulated in human cancers. However, little is known about the biological roles of TMPRSS4 in gastric cancer. In this study, we examined the effect of TMPRSS4 on gastric cancer cell proliferation, migration, and invasion. The expression and secretion of matrix metalloproteinase-9 (MMP-9) and activation of nuclear factor-κB (NF-κB) were determined. The involvement of NF-κB/MMP-9 signaling was checked. Our data showed that TMPRSS4 silencing significantly (P<0.05) reduced the migration and invasion of AGS and MKN-45 gastric cancer cells, without affecting cell proliferation. Overexpression of TMPRSS4 significantly promoted cell migration and invasion. The expression and secretion of MMP-9 was significantly (P<0.05) enhanced in TMPRSS4-overexpressing cells. TMPRSS4-overexpressing cells had a significantly (P<0.05) lower level of IκBα and higher level of nuclear NF-κB. Luciferase reporter assay confirmed that overexpression of TMPRSS4 resulted in a 3-5-fold increase in NF-κB-dependent luciferase activity. Downregulation of MMP-9 significantly (P<0.05) reversed the invasiveness of gastric cancer cells induced by TMPRSS4 overexpression. Moreover, pharmacological inhibition of NF-κB attenuated the invasion of TMPRSS4-overexpressing cells and the expression of MMP-9. Upregulation of TMPRSS4 enhances the invasiveness of gastric cancer cells, largely through activation of NF-κB and induction of MMP-9 expression. Our study provides the rationale for targeting TMPRSS4 in the treatment of gastric cancer.

[Clinical outcomes of radiofrequency ablation combined with transcatheter arterial chemoembolization for the treatment of hepatocellular carcinoma: a single-center experience].

OBJECTIVE: To compare the effect of radiofrequency ablation (RFA) combined with transcatheter arterial chemoembolization (TACE) with radiofrequency ablation alone for the treatment of 3 - 5 cm hepatocellular carcinoma (HCC). METHODS: From January 2006 to March 2010, sixty-two HCC patients were randomly treated with RFA combined with TACE (n = 32) or RFA alone (n = 30). This group included the patients who had Child-Pugh class A or B with three or fewer tumors, in which just one tumor size was 3 - 5 cm in diameter, and no evidence of extrahepatic tumor metastasis or macrovascular invasion. The follow up ranged from 9 to 39 months. Survival probabilities were estimated with the Kaplan-Meier method, and differences between survival curves were evaluated with the Log rank test. RESULTS: At the end of the study, the 1-, 2- and 3-year overall survival rates in the combined treatment group were 90.6%, 72%, and 53.1%, respectively, and in the radiofrequency ablation alone group were 83.3%, 56.75%, and 23.3%, respectively. The differences between the survival curves of the two groups were not statistically significant (P = 0.176). The 1-, 2-, and 3-year progress-free survival rates in the combined treatment group were 75.0%, 50.0%, and 34.3%, respectively, and in the radiofrequency ablation alone group were 63.3%, 33.3%, and 16.7%, respectively. The differences between the two groups were statistically significant (P = 0.027). The 1-, 2-, and 3-year local tumor progression rates in the combined treatment group were 12.5%, 18.75%, and 18.75% vs. 16.7%, 30%, and 36.6% in the radiofrequency ablation alone group, with a significant difference between the two groups (P = 0.047). CONCLUSION: Radiofrequency ablation plus TACE is better than radiofrequency ablation alone for the treatment of 3 - 5 cm hepatocellular carcinoma.