title: Neuropilin-1 is upregulated in hepatocellular carcinoma and contributes to tumour growth and vascular remodelling.
abstract: OBJECTIVE
  Neuropilin-1 (NRP1) is a transmembrane co-receptor for semaphorins and heparin-binding pro-angiogenic cytokines, principally members of the vascular endothelial growth factor family. Recent studies revealed an important role of NRP1 in angiogenesis and malignant progression of many cancers. The role of NRP1 in the development of hepatocellular carcinoma (HCC) is not completely understood.
  
  
  METHODS
  We used human tissue microarrays and a mouse transgenic model of HCC to establish the spatio-temporal patterns of NRP1 expression in HCC. To evaluate the therapeutic potential of targeting NRP1 in HCC, we treated HCC mice with peptide N, an NRP1 binding recombinant protein and competitive inhibitor of the VEGF-A(165)/NRP1 interaction.
  
  
  RESULTS
  We demonstrate that NRP1 is expressed in hepatic endothelial cells of both human healthy biopsies and in HCC samples, but not in normal hepatocytes. We found that increased NRP1 expression in human tumour hepatocytes is significantly associated with primary HCC. Using RT-PCR, Western blot and immunofluorescence analysis we show that NRP1 expression in the liver of transgenic HCC mice is increased with disease progression, in both vascular and tumour compartments. Blocking NRP1 function with peptide N leads to the inhibition of vascular remodelling and tumour liver growth in HCC mice.
  
  
  CONCLUSIONS
  Our results indicate a specific role of NRP1 in HCC growth and vascular remodelling and highlight the possibility of therapeutically targeting NRP1 for the treatment of HCC.
authors.affiliation: Institut des Vaisseaux et du Sang, Hôpital Lariboisière, Université Paris 7, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Bergé
authors.forename: David
authors.initials: D
authors.lastname: Allanic
authors.forename: Philippe
authors.initials: P
authors.lastname: Bonnin
authors.forename: Catherine
authors.initials: C
authors.lastname: de Montrion
authors.forename: Johann
authors.initials: J
authors.lastname: Richard
authors.forename: Michel
authors.initials: M
authors.lastname: Suc
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Boivin
authors.forename: Jean-Olivier
authors.initials: JO
authors.lastname: Contrerès
authors.forename: Brian P
authors.initials: BP
authors.lastname: Lockhart
authors.forename: Marc
authors.initials: M
authors.lastname: Pocard
authors.forename: Bernard I
authors.initials: BI
authors.lastname: Lévy
authors.forename: Gordon C
authors.initials: GC
authors.lastname: Tucker
authors.forename: Gérard
authors.initials: G
authors.lastname: Tobelem
authors.forename: Tatyana
authors.initials: T
authors.lastname: Merkulova-Rainon
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D056945:Hep G2 Cells; D017228:Hepatocyte Growth Factor / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D039942:Neuropilin-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D015854:Up-Regulation / Q000502:physiology
chemical_list: C066855:HGF protein, human; D010455:Peptides; D039942:Neuropilin-1; D017228:Hepatocyte Growth Factor