Paradoxical pro-invasive effect of the serine proteinase inhibitor tissue factor pathway inhibitor-2 on human hepatocellular carcinoma cells.
J Biol Chem
; 275(45): 35565-9, 2000 Nov 10.
Article
in En
| MEDLINE
| ID: mdl-10954721
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pregnancy Proteins
/
Glycoproteins
/
Serine Proteinase Inhibitors
/
Carcinoma, Hepatocellular
Limits:
Animals
/
Humans
Language:
En
Journal:
J Biol Chem
Year:
2000
Document type:
Article
Affiliation country:
Francia