Paradoxical pro-invasive effect of the serine proteinase inhibitor tissue factor pathway inhibitor-2 on human hepatocellular carcinoma cells.

Abstract

We have previously shown that human liver myofibroblasts promote in vitro invasion of human hepatocellular carcinoma (HCC) cells through a hepatocyte growth factor (HGF)/urokinase/plasmin-dependent mechanism. In this study, we demonstrate that myofibroblasts synthesize the serine proteinase inhibitor tissue factor pathway inhibitor-2 (TFPI-2). Despite the fact that recombinant TFPI-2 readily inhibits plasmin, we show that it potentiates HGF-induced invasion of HCC cells and is capable of inducing invasion on its own. Furthermore, HCC cells stably transfected with a TFPI-2 expression vector became spontaneously invasive. HCC cells express tissue factor and specifically factor VII. Addition of an antibody to factor VII abolished the pro-invasive effect of TFPI-2. We suggest that TFPI-2 induces invasion following binding to a tissue factor-factor VIIa complex preformed on HCC cells. Our data thus demonstrate an original mechanism of cell invasion that may be specific for liver tumor cells.

• Authors: V Neaud, T Hisaka, A Monvoisin, C Bedin, C Balabaud, D C Foster, A Desmoulière, W Kisiel, J Rosenbaum
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 275 Issue 45 Pg. 35565-9 (Nov 10 2000) ISSN: 0021-9258 [Print] United States
• PMID: 10954721 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• DNA, Complementary
• Glycoproteins
• Pregnancy Proteins
• Protein Isoforms
• Recombinant Proteins
• Serine Proteinase Inhibitors
• tissue-factor-pathway inhibitor 2
• Factor VII
• Thromboplastin
• Mitogen-Activated Protein Kinases
• Fibrinolysin

Topics

• Animals
• Blotting, Northern
• Carcinoma, Hepatocellular (enzymology)
• Cell Division
• Cell Line
• Cricetinae
• DNA, Complementary (metabolism)
• Dose-Response Relationship, Drug
• Factor VII (metabolism)
• Fibrinolysin (antagonists & inhibitors, metabolism)
• Gene Library
• Glycoproteins (chemistry, metabolism)
• Humans
• Liver (metabolism)
• Liver Neoplasms (enzymology)
• MAP Kinase Signaling System
• Mitogen-Activated Protein Kinases (metabolism)
• Neoplasm Invasiveness
• Phosphorylation
• Pregnancy Proteins (chemistry, metabolism)
• Protein Isoforms
• Recombinant Proteins (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Serine Proteinase Inhibitors (chemistry, metabolism)
• Thromboplastin (metabolism)
• Transfection
• Tumor Cells, Cultured