| Project/Area Number |
12219211
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Osaka University |
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Principal Investigator |
MIYASAKA Masayuki Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (50064613)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Toshiyuki Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助教授 (30217054)
HIRATA Takako Osaka University, Research Institute for Microbial diseases, Assistant Professor, 微生物病研究所, 特任助教授 (00346199)
村井 稔幸 大阪大学, 医学系研究科, 助手 (20311756)
川島 博人 大阪大学, 医学系研究科, 助手 (50260336)
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| Project Period (FY) |
2000 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥157,100,000 (Direct Cost: ¥157,100,000)
Fiscal Year 2004: ¥33,000,000 (Direct Cost: ¥33,000,000)
Fiscal Year 2003: ¥36,000,000 (Direct Cost: ¥36,000,000)
Fiscal Year 2002: ¥28,000,000 (Direct Cost: ¥28,000,000)
Fiscal Year 2001: ¥32,500,000 (Direct Cost: ¥32,500,000)
Fiscal Year 2000: ¥27,600,000 (Direct Cost: ¥27,600,000)
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| Keywords | CD44 / hyaluronic acid / hyaluronidase / P-selectin / PSG L-1 / extracellular matrix / metastasis / グリコサミノグリカン / 細胞接着 / 血管内皮細胞 / 癌転移 / セレクチン / リポソーム / 癌細胞ローリング / 血行性転移 / プロテオグリカン |
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| Research Abstract |
We have found that a tumor metastasis-related cell surface molecule CD44 can recognize not only hyaluronic acid (GlcA-GlcNAc) but also an essential moiety of chondroitin sulfate, GlcA/Ido-A-GaINAc. This indicates that CD44 can interact with various proteoglycans expressed by vascular endothelial cells as well as extracellular matrix (ECM) components. In addition, we found that hyaluronan (HA) degraded into oligosaccharides of a certain size range can induce proteolytic cleavage of CD44 from tumor cells and promote tumor cell motility. Furthermore, we found that tumor cells themselves produce hyaluronidases that can generate HA oligosaccharides, which in turn bind to tumor cell CD44 to promote CD44 cleavage and tumor motility. Other types of glycosaminoglycans also showed similar activities when they were degraded into oligomers. These results suggest that tumor cells and their ECMs can generate substances that promote tumor cell invasion. We have also made investigations on chemokines and chemokine binding molecules and found that chemokines can induce directional cell motility efficiently when they are immobilized on certain ECM components.
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