|Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
Purpose: The effect of irradiation on tumor adhesiveness, invasiveness, motility and angiogenesis was investigated to determine the scientific and quantitative data on how safety margin of irradiation around gross tumor should be set. Methods and Materials: The cancer cells such as CHO, PC-3, DU145, SAS/neo, SA5/mp53, HT1080, HT1080-mA9, MAG-F5, YKG-1 were irradiated with X-ray to evaluate tumor adhesiveness, invasiveness and motility quantitatively. HT1080 and DU145 were irradiated with carbon ion and proton beams to evaluate the same functions as well as activity of MMP-2, regulation of MT1-MMP1 and TIMP2, compared with those with X-ray. ECV304 and HUVEC were irradiated with carbon ion and proton beams to evaluate angiogenesis, compared with those with X-ray. Results: (1) Most cancer cells increased their invasiveness and metastatic potential even by sublethal doses of X-ray irradiation. (2) On the other hand, carbon and proton beams inhibited invasiveness significantly. Slight depression of activity of MMP-2, down-regulation of MT1-MMP1 and up-regulation of TIMP2 were observed simultaneously. (3) Angiogenesis was also inhibited even by sublethal doses of carbon and proton beam irradiation. Conclusion: Xray irradiation increased the tumor invasiveness, metastatic potential and angiogenesis at sublethal dose area on field margin. Carbon ion and proton irradiation inhibited those functions. Therefore, careful setting of field margin in X-ray treatment is essential and these quantitative data by each cancer are very important. Because the effectiveness of carbon ion and proton breams was clear in terms of inhibition of tumor invasiveness and metastasis, the upstream molecular mechanisms are investigated intensively.