Functional expression of a proliferation-related ligand in hepatocellular carcinoma and its implications for neovascularization.
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.
Okano
Hiroshi
H
First Department of Internal Medicine, Mie University School of Medicine, Tsu, Mie 514-8507, Japan.
Shiraki
Katsuya
K
Yamanaka
Yutaka
Y
Inoue
Hidekazu
H
Kawakita
Tomoyuki
T
Saitou
Yukiko
Y
Yamaguchi
Yumi
Y
Enokimura
Naoyuki
N
Ito
Keiichi
K
Yamamoto
Norihiko
N
Sugimoto
Kazushi
K
Murata
Kazumoto
K
Nakano
Takeshi
T
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
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