Tissue factor pathway inhibitor-2 silencing promotes hepatocellular carcinoma cell invasion in vitro.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death in the world and metastasis is an essential aspect of HCC progression. Tissue factor pathway inhibitor-2 (TFPI-2) has been implicated as a potential suppressor gene to regulate tumor invasion and metastasis. In this study, we silenced TFPI-2 in the HCC cell line MHCC97-L and evaluated the role of TFPI-2 in cell invasion and its impact on gene expression. We showed in this study that stable TFPI-2 downregulation in MHCC97-L cells resulted in increased cell adhesion and invasion. We also showed that mRNA and protein expression levels of MMP-1/3, CD44, and ICAM-1 were increased, while those of MMP-2/9 were not changed by TFPI-2 silencing. Furthermore, silencing of TFPI-2 caused increased Akt phosphorylation level and NF-κB transcription in MHCC97-L cells. In conclusion, this study confirms that TFPI-2 downregulation can contribute to tumor invasion of HCC cells through alteration in the expression of metastasis-related genes. Anat Rec, 296:1708–1716, 2013. © 2013 Wiley Periodicals, Inc.