Basic fibroblast growth factor regulates proliferation and motility of human hepatoma cells by an autocrine mechanism.
OBJECTIVE
Basic fibroblast growth factor has mitogenic and angiogenic properties. In this study, we aimed to evaluate the role of fibroblast growth factor in the development and progression of human hepatocellular carcinoma.


METHODS
The expression of basic fibroblast growth factor, fibroblast growth factor receptor-1, and a receptor isoform was investigated by in situ hybridization, immunohistochemistry, reverse transcription-polymerase chain reaction, Western blot analysis and confocal laser-scanning microscopy. The influence of exogenous basic fibroblast growth factor on DNA synthesis and motility of human hepatoma cells were also evaluated.


RESULTS
Basic fibroblast growth factor and fibroblast growth factor receptor-1 messenger RNAs were present mainly in tumor cells and less so in hepatocytes from noncancerous liver tissue. Immunoreactive products of basic fibroblast growth factor and fibroblast growth factor receptor-1 were observed in tumor cells. The isoform IIIc was expressed in hepatocellular carcinoma tissue and hepatoma cell lines. Exogenous basic fibroblast growth factor stimulated DNA synthesis and motility of hepatoma cells. The effect was more marked in poorly-differentiated hepatoma cells than in well-differentiated hepatoma cells. Fibroblast growth factor-1 expression on hepatoma cells was also more marked in poorly-differentiated hepatoma cells than in well-differentiated hepatoma cells. The stimulated motility on basic fibroblast growth factor was suppressed by an anti-fibroblast growth factor receptor-1 antibody.


CONCLUSIONS
Basic fibroblast growth factor may play an important role in the development and progression of hepatocellular carcinoma via an autocrine mechanism involving fibroblast growth factor and its receptor.
Kin
M
M
Second Department of Medicine, Kurume University School of Medicine, Japan.
Sata
M
M
Ueno
T
T
Torimura
T
T
Inuzuka
S
S
Tsuji
R
R
Sujaku
K
K
Sakamoto
M
M
Sugawara
H
H
Tamaki
S
S
Tanikawa
K
K
D000328:Adult; D000368:Aged; D017398:Alternative Splicing; D019898:Autocrine Communication; D015153:Blotting, Western; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008099:Liver / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D008934:Mitogens / Q000502:physiology; D016133:Polymerase Chain Reaction / Q000379:methods; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000502:physiology*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D008934:Mitogens; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; C496348:FGFR1 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1