The placental growth factor as a target against hepatocellular carcinoma in a diethylnitrosamine-induced mouse model.

Abstract

BACKGROUND & AIMS:

The placental growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family known to stimulate endothelial cell growth, migration and survival, attract angiocompetent macrophages, and determine the metastatic niche. Unlike VEGF, genetic studies have shown that PlGF is specifically involved in pathologic angiogenesis, thus its inhibition would not affect healthy blood vessels, providing an attractive drug candidate with a good safety profile.

METHODS:

We assess whether inhibition of PlGF could be used as a potential therapy against hepatocellular carcinoma (HCC), by using PlGF knockout mice and monoclonal anti-PlGF antibodies in a mouse model for HCC. In addition, the effect of PlGF antibodies is compared to that of sorafenib, as well as the combination of both therapies.

RESULTS:

We have found that both in a transgenic knockout model and in a treatment model, targeting PlGF significantly decreases tumor burden. This was achieved not only by inhibiting neovascularisation, but also by decreasing hepatic macrophage recruitment and by normalising the remaining blood vessels, thereby decreasing hypoxia and reducing the prometastatic potential of HCC.

CONCLUSIONS:

Considering the favourable safety profile and its pleiotropic effect on vascularisation, metastasis and inflammation, PlGF inhibition could become a valuable therapeutic strategy against HCC.

• Authors: Femke Heindryckx, Stephanie Coulon, Ellen Terrie, Christophe Casteleyn, Jean-Marie Stassen, Anja Geerts, Louis Libbrecht, Joke Allemeersch, Peter Carmeliet, Isabelle Colle, Hans Van Vlierberghe
• Journal: Journal of hepatology (J Hepatol) Vol. 58 Issue 2 Pg. 319-28 (Feb 2013) ISSN: 1600-0641 [Electronic] Netherlands
• PMID: 23046674 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Chemical References

• Antibodies, Monoclonal
• Antineoplastic Agents
• Pgf protein, mouse
• Phenylurea Compounds
• Pregnancy Proteins
• Placenta Growth Factor
• Niacinamide
• Diethylnitrosamine
• Sorafenib

Topics

• Animals
• Antibodies, Monoclonal (immunology, pharmacology, therapeutic use)
• Antineoplastic Agents (pharmacology, therapeutic use)
• Carcinoma, Hepatocellular (chemically induced, drug therapy, physiopathology)
• Diethylnitrosamine (adverse effects)
• Disease Models, Animal
• Drug Therapy, Combination
• Liver Neoplasms (chemically induced, drug therapy, physiopathology)
• Mice
• Mice, Knockout
• Mice, Transgenic
• Neoplasm Metastasis (drug therapy, physiopathology)
• Neovascularization, Pathologic (drug therapy, physiopathology)
• Niacinamide (analogs & derivatives, pharmacology, therapeutic use)
• Phenylurea Compounds (pharmacology, therapeutic use)
• Placenta Growth Factor
• Pregnancy Proteins (deficiency, immunology, physiology)
• Sorafenib
• Treatment Outcome