Project/Area Number |
17K11828
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Surgical dentistry
|
Research Institution | Tokyo Medical and Dental University |
Principal Investigator |
|
Co-Investigator(Kenkyū-buntansha) |
渡部 徹郎 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (00334235)
|
Project Period (FY) |
2017-04-01 – 2021-03-31
|
Project Status |
Completed (Fiscal Year 2020)
|
Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Keywords | エクソソーム / プロテオグリカン |
Outline of Final Research Achievements |
Cancer cell-derived exosomes, small extracellular vesicles have been reported to play an important role in cancer progression by affecting the function of cells residing in the cancer microenvironment. Exosomes, can promote tumor progression by stimulating various processes including EMT and are considered as a promising target for cancer treatment. Heparan sulfate proteoglycan (HSPG) has been reported to be involved in the formation and uptake of exosomes. We aimed to elucidate the function and mechanism of HSPG in epithelial-mesenchymal transition (EMT) of oral cancer and uptake of cancer cell-derived exosomes. Oral squamous cell carcinoma cell lines treated with TGF-β underwent EMT, became more motile and secreted more exosomes than control cells. These exosomes contained multiple HSPGs sand were able to induce endothelial-mesenchymal transition of vascular endothelial cells.
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Academic Significance and Societal Importance of the Research Achievements |
口腔がんはリンパ節への転移が起こりやすいため、予後不良に陥りやすい。がんの治療法としては、手術治療が中心となり、患者の生活の質(QOL: quality of life)が低下することが問題となっている。本研究の最終的な目標は、エクソソームを標的とした創薬をめざすことであり、今までになかった非侵襲的かつ効果的な治療法を確立することである。本研究の成果により、口腔がん由来のエクソソーム に特異的に存在するタンパク質を同定することで、エクソソームを標的とした、未だに発見が難しい口腔がんの早期診断が可能となり、その臨床応用的な意義は大きい。
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