title: Functional expression of a proliferation-related ligand in hepatocellular carcinoma and its implications for neovascularization.
abstract: OBJECTIVE
  To detect the expression of a proliferation-related ligand on human hepatocellular carcinoma (HCC) cell lines (SK-Hep1, HLE and HepG2) and in culture medium.
  
  
  METHODS
  APRIL expression was analyzed by Western blotting in HCC cell lines. Effects of APRIL to cell count and angiogenesis were analyzed, too.
  
  
  RESULTS
  Recombinant human APRIL (rhAPRIL) increased cell viability of HepG2 cells and, in HUVEC, rhAPRIL provided slight tolerance to cell death from serum starvation. Soluble APRIL (sAPRIL) from HLE cells increased after serum starvation, but did not change in SK-Hep1 or HepG2 cells. These cells showed down-regulation of VEGF after incubation with anti-APRIL antibody. Furthermore, culture medium from the HCC cells treated with anti-APRIL antibody treatment inhibited tube formation of HUVECs.
  
  
  CONCLUSIONS
  Functional expression of APRIL might contribute to neovascularization via an upregulation of VEGF in HCC.
authors.affiliation: First Department of Internal Medicine, Mie University School of Medicine, Tsu, Mie 514-8507, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Okano
authors.forename: Katsuya
authors.initials: K
authors.lastname: Shiraki
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yamanaka
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Inoue
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kawakita
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Saitou
authors.forename: Yumi
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Enokimura
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ito
authors.forename: Norihiko
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Kazushi
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Kazumoto
authors.initials: K
authors.lastname: Murata
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakano
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008113:Liver Neoplasms / Q000098:blood supply / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D011994:Recombinant Proteins / Q000494:pharmacology; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D008024:Ligands; D008565:Membrane Proteins; D011994:Recombinant Proteins; C114631:TNFSF13 protein, human; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A