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

Anat Rec (Hoboken). 2013 Nov;296(11):1708-16. doi: 10.1002/ar.22789.

Abstract

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.

Keywords: hepatocellular carcinoma; invasion; tissue factor pathway inhibitor-2.

MeSH terms

  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / physiopathology
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation
  • Down-Regulation / drug effects
  • Gene Silencing / drug effects
  • Glycoproteins / antagonists & inhibitors*
  • Glycoproteins / drug effects
  • Glycoproteins / genetics*
  • Humans
  • In Vitro Techniques
  • Intercellular Adhesion Molecule-1 / metabolism
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Liver Neoplasms / physiopathology
  • NF-kappa B / metabolism
  • Neoplasm Invasiveness / pathology
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Small Interfering / pharmacology

Substances

  • Glycoproteins
  • NF-kappa B
  • RNA, Small Interfering
  • tissue-factor-pathway inhibitor 2
  • Intercellular Adhesion Molecule-1
  • Proto-Oncogene Proteins c-akt