| Project/Area Number |
16K12900
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Biomedical engineering/Biomaterial science and engineering
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| Research Institution | Yokohama City University |
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Principal Investigator |
Higashi Shouichi 横浜市立大学, 生命ナノシステム科学研究科(八景キャンパス), 教授 (10275076)
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| Co-Investigator(Renkei-kenkyūsha) |
KIMURA YAYOI 横浜市立大学, 先端医科学研究センター, 准教授 (80391936)
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | MMP-7 / HAI-1 / がん転移 / 細胞間接着 / 細胞凝集 / コレステロール硫酸 / 細胞表層プロテオリシス / がん転移抑制剤 / PKDドメイン / オリゴペプチド / マトリックスメタロプロテアーゼ / 大腸がん / 転移 / 再生医療 |
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| Outline of Final Research Achievements |
(1) We found that hepatocyte growth factor activator inhibitor type 1 (HAI-1), a membrane-bound Kunitz-type serine protease inhibitor, is an MMP-7 substrate; MMP-7 cleaves HAI-1 at the membrane-proximal region, and releases the extracellular region as soluble HAI-1(sHAI-1).
(2) The released sHAI-1, but not the membrane-bound HAI-1, has an ability to induce cancer cell aggregation, and the HAI-1 region corresponding to amino acids 141-249 is essential for the cell aggregation-inducing activity.
(3) A cell-surface cholesterol sulfate-independent proteolytic action of MMP-7 is critical for the sHAI-1-mediated induction of cell aggregation, whereas cholesterol sulfate is needed for the MMP-7-catalyzed generation of sHAI-1.
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