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Synergistic effect of basic fibroblast growth factor and vascular endothelial growth factor in murine hepatocellular carcinoma
Author(s) -
Yoshiji Hitoshi,
Kuriyama Shigeki,
Yoshii Junichi,
Ikenaka Yasuhide,
Noguchi Ryuichi,
Hicklin Daniel J.,
Huber James,
Nakatani Toshiya,
Tsujinoue Hirohisa,
Yanase Koji,
Imazu Hiroo,
Fukui Hiroshi
Publication year - 2002
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1053/jhep.2002.32541
Subject(s) - angiogenesis , basic fibroblast growth factor , vascular endothelial growth factor , cancer research , in vivo , vascular endothelial growth factor a , biology , fibroblast growth factor , growth factor , medicine , vegf receptors , receptor , microbiology and biotechnology
The growth of any solid tumor depends on angiogenesis. Among the known angiogenic factors, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), are potent and representative factors involved in tumor development. It has been reported that bFGF and VEGF showed a synergistic effect in both in vitro and in vivo angiogenesis. However, the interaction of these factors on tumor development and angiogenesis, including hepatocellular carcinoma (HCC), has not yet been elucidated. In this study, we examined the combined effect of bFGF and VEGF overexpression by means of a combination of a retroviral tetracycline (tet)–regulated (Retro‐Tet) gene expression system, which can manipulate the gene expression in vivo by providing tet in the drinking water, and a conventional plasmid gene expression system. In an allograft study, bFGF and VEGF overexpression synergistically increased tumor growth and angiogenesis in the murine HCC cells. This synergistic effect also was found in established tumors. VEGF messenger RNA (mRNA) expression in the tumor was increased 3.1‐fold by bFGF‐overexpression, and the bFGF‐induced tumor development was significantly attenuated by treatment with KDR/Flk‐1 neutralizing monoclonal antibody. In conclusion, these results suggest that bFGF synergistically augments VEGF‐mediated HCC development and angiogenesis at least partly by induction of VEGF through KDR/Flk‐1.