title: The placental growth factor as a target against hepatocellular carcinoma in a diethylnitrosamine-induced mouse model.
abstract: OBJECTIVE
  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.affiliation: Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Femke
authors.initials: F
authors.lastname: Heindryckx
authors.forename: Stephanie
authors.initials: S
authors.lastname: Coulon
authors.forename: Ellen
authors.initials: E
authors.lastname: Terrie
authors.forename: Christophe
authors.initials: C
authors.lastname: Casteleyn
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Stassen
authors.forename: Anja
authors.initials: A
authors.lastname: Geerts
authors.forename: Louis
authors.initials: L
authors.lastname: Libbrecht
authors.forename: Joke
authors.initials: J
authors.lastname: Allemeersch
authors.forename: Peter
authors.initials: P
authors.lastname: Carmeliet
authors.forename: Isabelle
authors.initials: I
authors.lastname: Colle
authors.forename: Hans
authors.initials: H
authors.lastname: Van Vlierberghe
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology*; D004052:Diethylnitrosamine / Q000009:adverse effects*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000503:physiopathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000503:physiopathology; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000494:pharmacology / Q000627:therapeutic use; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000172:deficiency / Q000276:immunology / Q000502:physiology*; D000077157:Sorafenib; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C000608037:Pgf protein, mouse; D010671:Phenylurea Compounds; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; D009536:Niacinamide; D004052:Diethylnitrosamine; D000077157:Sorafenib