| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
We performed this study to investigate the mechanisms of tumor angiogenesis in oral cancer, and to explore a novel therapeutic strategies. Using the rabbit cornea assay, we examined the role of hepatocyte growth factor (HGF) in tumor angiogenesis. 1) recombinant HGF induced angiogenesis. 2) anti-HGF antibody inhibited the angiogenic activity induced by a small pellet of VX2 carcinoma of the tongue. These results suggest that HGF play an important role in tumor angiogenesis in VX2 carcinoma of the tongue. In the specimens from oral cancer patients, expression of c-Met, the known receptor for HGF, was commonly expressed in small vessels adjacent to the tumor nest, implying that HGF/c-Met signaling system is involved in tumor ngiogenesis in oral cancer. In addition, we tested the hypotheses that HGF stimulates expressions of the known receptors of vascular endothelial growth factor (VEGF), Fit-1 and Elk, and the adhesion molecules, I-CAM-1 and V-CAM-1, which are considered to mediate cancer metastasis. By ELIZA assay, we failed to detect a significant increase in expression of these molecules after HGF stimulation. We also evaluated anti-tumor effects of an angiogenesis inhibitor in oral cancer. TNP-470 showed a marked inhibitory effect against the rabbit bearing VX2 carcinoma of the tongue, suggesting that angiogenesis inhibitors have promising therapeutic uses for oral cancer. From these data, we may conclude that HGF is involved in tumor angiogenesis of the oral cancer, playing an important role for the tumor progression. Then, we will be studying anti-tumor effects of the inhibitor for HOF/c-Met signaling system and its advantages for clinical use.
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