Tissue factor pathway inhibitor-2 inhibits the growth and invasion of hepatocellular carcinoma cells and is inactivated in human hepatocellular carcinoma

Human tissue factor pathway inhibitor-2 (TFPI-2) is an extracellular matrix-associated Kunitz-type serine proteinase inhibitor that inhibits the plasmin- and trypsin-mediated activation of matrix metalloproteinases and inhibits tumor progression, invasion and metastasis. Previous studies have shown that TFPI-2 is downregulated in the progression of various tumors. The purpose of this study was to investigate the expression and function of TFPI-2 in hepatocellular carcinoma (HCC). In situ hybridization was used to detect human TFPI-2 mRNA and immunohistochemistry was performed to examine the role of TFPI-2 expression in hepatocarcinoma tissues. Cell proliferation was assessed using MTT assay. In situ hybridization and immunohistochemical analyses revealed that the expression of TFPI-2 in hepatocarcinoma tissues was markedly lower than that in tumor-adjacent normal hepatic tissues. Restored expression of TFPI-2 in HepG2 cells inhibits cell proliferation and invasion. Taken together, the results suggest that TFPI-2 has a tumor-suppression action and its inactivation may contribute to HCC.