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

Yong Xu

doi:10.3892/ol.2011.340

Abstract

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. Insitu 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 HepG(2) 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.

Highlights

Hepatocellular carcinoma (HCC) is one of the most common primary tumors worldwide [1], and is prevalent in China
In situ hybridization with Tissue factor pathway inhibitor‐2 (TFPI-2) probe detected little or no TFPI-2 mRNA in hepatocarcinoma tissue sections, whereas a high level of TFPI-2 mRNA was detected in tumoradjacent normal hepatic tissue sections (Fig. 1A and B)
Further immunohistochemical analysis confirmed that TFPI-2 protein was stained strongly positive in normal hepatic tissues but was weakly stained in hepatocarcinoma tissues (Fig. 1C and D)

Summary

Introduction

Hepatocellular carcinoma (HCC) is one of the most common primary tumors worldwide [1], and is prevalent in China. It is a major complication of liver cirrhosis. TFPI-2 is abundantly expressed in full-term placenta and is widely expressed in a variety of adult human tissues such as liver, skeletal, muscle, heart, kidney and pancreas [11,12,13]. It is mainly synthesized and secreted into the ECM by a wide variety of cells. TFPI-2 is thought to regulate the plasmin- and trypsin-mediated activation of matrix pro-metalloproteinases and play a significant role in the regulation of ECM degradation, which is an essential step for cell remodeling, as well as tumor cell invasion and metastasis [14]

Objectives

Methods

Results

Conclusion