| Project/Area Number |
15390558
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional basic dentistry
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| Research Institution | TOKYO MEDICAL AND DENTAL UNIVERSITY |
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Principal Investigator |
MORITA Ikuo GRADUATE SCHOOL TOKYO MEDICAL AND DENTAL UNIVERSITY, CELLULAR PHYSIOLOGICAL CHEMISTRY, PROFESSOR, 大学院・医歯学総合研究科, 教授 (60100129)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAHAMA Ken-ichi GRADUATE SCHOOL TOKYO MEDICAL AND DENTAL UNIVERSITY, CELLULAR PHYSIOLOGICAL CHEMISTRY, ASSOCIATE PROFESSOR, 大学院・医歯学総合研究科, 助教授 (60281515)
ODA Shigeru GRADUATE SCHOOL TOKYO MEDICAL AND DENTAL UNIVERSITY, PERIODONTOLOGY, LECTURER, 大学院・医歯学総合研究科, 講師 (70160869)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 2004: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2003: ¥11,100,000 (Direct Cost: ¥11,100,000)
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| Keywords | Angiogenesis / PEDF / VEGF / oral squamous cell carcinoma / collagen-binding site / age-related macular degeneration / 血管新生抑制 / アミロイドβ / 血管内皮細胞 / PFDF / VEGF / 老化 / 扁平上皮ガン |
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| Research Abstract |
The objectives in this study are to regulate oral cancer and to establish the method for repair in oral function by controlling angiogenesis. In this research, we examined the regulation mechanism for PEDF production and the molecular mechanism for anti-angiogenic activity of PEDF. When the human oral squamous cell carcinoma cell lines were exposed by ischemia, PEDF production was up-regulated, in contrast, PEDF was down-regulated by ischemia in normal cells. In ischemia, VEGF was up-regulated and this VEGF stimulated PEDF production via PEDFR-1. It is interesting that PEDF/VEGF ratio increased in benign tumor, but decreased dramatically in cancer. These results suggest that in cancer the low PEDF/VEGF ratio causes to angiogenesis in cancer tissue, and the part of angiogenesis is escaped from ischemia, which leads to decrease PEDF production. Next, we investigated here the possibility the involvement of the motif for ECM interaction in anti-angiogenic activity of PEDF. The growth rates of HeLa cells in culture were not affected by transfection of PEDF, indicating that PEDF did not suppress tumor cell growth directly. In tumor xenografts, overexpression of wild-type PEDF significantly suppressed tumor growth, whereas the mutant of collagen I-binding site of PEDF (Col-mut PEDF) did not inhibit tumor growth. The mutant of heparin-binding site of PEDF (Hep-mut PEDF) suppressed tumor growth. Histological analysis showed that the density and area of microvasculatures in either PEDF or Hep-mut PEDF were suppressed as compared with those in either vector or Col-mut PEDF. Our data indicate that PEDF inhibits tumor growth via anti-angiogenic activity, and the collagen I -binding motif of PEDF is involved in the biological activity. We also examined the cloning of PEDF receptor using by expression cloning technique. We got several genes to bind for PEDF, and we have examined whether these proteins was a receptor for PEDF.
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