Significance of Vascular Endothelial Growth Factor in Tumor Progression and Metastasis of Human Colorectal Cancer

Yoko Kondo¹⁾²⁾, Shigeki Arii¹⁾, Akira Mori¹⁾ and Masayuki Imamura¹⁾

¹⁾Department of Surgery & Surgical Basic Science, Graduate School of Medicine, Kyoto University

²⁾Division of Gastroenterology and Hepatology, Department of Internal Medicine, Graduate School of Medicine, Kyoto University

Expression of vascular endothelial growth factor (VEGF) in 133 colorectal tumor specimens comprised of 27 adenomas, 46 early colorectal carcinomas, 60 advanced colorectal carcinomas was evaluated by RT-PCR, Northern blot hybridization, and was immunohistochemistry. Tumor angiogenesis paralleled tumor development, and partially associated with VEGF expression, in colorectal adenomas and the early stages of human colorectal cancer. Expression of VEGF mRNA in advanced colorectal carcinomas was correlated with tumor progression, including metastasis. We attempted to clarify the role of VEGF in the tumor growth, neovascularization, and metastasis of human colon cancer by using cells transfected with the VEGF gene. We found that sense-VEGF transfectants have a growth advantage due to vigorous tumor angiogenesis. We also demonstrated that sense-VEGF transfectants metastasized to the liver and had greater potential to induce peritoneal dissemination. In conclusion, the present study provided clear evidence that VEGF plays an important role in cancer growth by stimulating neovascularization and subsequent metastasis.

Key words
colorectal cancer, vascular endothelial growth factor, angiogenesis

Reprint requests
Yoko Kondo Department of Surgery & Surgical Basic Science Graduate School of Medicine Kyoto University, 54-Shogoin Kawara-cho, Sakyo-ku, Kyoto, 606-8507 JAPAN

Accepted
December 22, 1999

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