Vascular endothelial growth factor tightly regulates in vivo development of murine hepatocellular carcinoma cells

✍ Scribed by Hitoshi Yoshiji; Shigeki Kuriyama; Junichi Yoshii; Masaharu Yamazaki; Masaji Kikukawa; Hirohisa Tsujinoue; Toshiya Nakatani; Hiroshi Fukui

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 241 KB
• Volume: 28
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.510280607

✦ Synopsis

Angiogenesis is essential for the development of a solid tumor, including hepatocellular carcinoma (HCC). HCC is

a well-known hypervascular tumor. Vascular endothelial growth factor (VEGF) is one of the most potent angiogenic factors. Its role has not been clarified in vivo in HCC development. We used a self-contained, tetracyclineregulated retroviral vector system to elucidate the effect of VEGF on murine HCC development in a xenograft experimental model. By delivering the VEGF gene within the retroviral vector and under the control of a tetracyclineregulated promoter, we were able to manipulate VEGF expression in vivo tumor by providing tetracycline in the drinking water. Overexpression of VEGF showed a marked increase in tumor development accompanied by augmentation of neovascularization. The degree of tumor enlargement corresponded to the level of VEGF gene expression. Suppression of VEGF led to a decrease in tumor growth at the established tumor size, whether relatively small or large. The level of VEGF expression did not alter the proliferation of HCC cells in vitro. In a double-chamber chemoinvasion assay, the in vitro invasion activity of VEGFtransduced cells was not changed. In the presence of endothelial cells (EC), however, VEGF-transduced cells showed a marked increase in their in vitro invasion activity. These results suggested that VEGF plays a critical role in the development of HCC in cooperation with EC (HEPATOL-