title: Inhibition of the placental growth factor decreases burden of cholangiocarcinoma and hepatocellular carcinoma in a transgenic mouse model.
abstract: OBJECTIVE
  Hepatocellular carcinoma and cholangiocarcinoma form the majority of primary hepatic tumours and are the third most common cause of cancer-related deaths. These liver tumours rapidly outgrow their vascular supply and become hypoxic, resulting in the production of hypoxia inducible factors and triggering the angiogenic switch. Therefore, inhibiting angiogenesis has proven to be a valuable therapeutic strategy in hepatocellular carcinoma, yet less is known about its use in cholangiocarcinoma. In this study, we assess whether inhibiting the placental growth factor (PlGF) could offer a therapeutic option in mice with hepatocellular carcinoma and cholangiocarcinoma. PlGF is a homologue of the vascular endothelial growth factor, which is only involved in pathological angiogenesis, therefore, its inhibition does not induce adverse effects.
  
  
  METHODS
  We have used a chemically induced transgenic mouse model in which both hepatocellular carcinoma and cholangiocarcinoma develop after 25 weeks and are treated with murine monoclonal antibodies targeting PlGF.
  
  
  RESULTS
  This study has shown for the first time that inhibiting PlGF decreases the burden of cholangiocarcinoma, by affecting both angiogenesis and inflammation.
  
  
  CONCLUSIONS
  The use of monoclonal antibodies targeting PlGF could thus offer a potential systemic treatment for patients who suffer from primary liver tumours.
authors: Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium.
authors: Femke
authors: F
authors: Heindryckx
authors: Eliene
authors: E
authors: Bogaerts
authors: Stephanie H
authors: SH
authors: Coulon
authors: Hilde
authors: H
authors: Devlies
authors: Anja M
authors: AM
authors: Geerts
authors: Louis
authors: L
authors: Libbrecht
authors: Jean Marie
authors: JM
authors: Stassen
authors: Peter
authors: P
authors: Carmeliet
authors: Isabelle O
authors: IO
authors: Colle
authors: Hans R
authors: HR
authors: Van Vlierberghe
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001650:Bile Duct Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D018281:Cholangiocarcinoma / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000037:antagonists & inhibitors*; D011393:Procollagen-Proline Dioxygenase / Q000235:genetics; D016896:Treatment Outcome; D047368:Tumor Burden
chemical_list: D000911:Antibodies, Monoclonal; C000608037:Pgf protein, mouse; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; D011393:Procollagen-Proline Dioxygenase; C490189:Egln1 protein, mouse; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases