Exosomes promoting malignancy and affecting tumor microenvironment, the target for anti-tumor therapy.
| Project/Area Number |
17K11828
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
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| 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)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| 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)
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| Keywords | エクソソーム / プロテオグリカン |
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| 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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Report
(5 results)
Research Products
(21 results)
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[Journal Article] TNF-α enhances TGF-β-induced endothelial-to-mesenchymal transition via TGF-β signal augmentation2020
Author(s)
Yasuhiro Yoshimatsu, Ikumi Wakabayashi, Shiori Kimuro, Naoya Takahashi, Kazuki Takahashi, Miho Kobayashi, Nako Maishi, Katarzyna A. Podyma-Inoue, Kyoko Hida, Kohei Miyazono, Tetsuro Watabe
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Journal Title
Cancer Sciense
Volume: -
Issue: 7
Pages: 2385-2399
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Oral squamous carcinoma cells under TGF-β-induced cell cycle arrest represent highly motile and invasive population2020
Author(s)
Katarzyna A. Inoue, Kazuki Takahashi, Maki Saito, Atsushi Kaida, Akinari Sugauchi, Toshihiro Uchihashi, Yasuhiro Yoshimatsu, Susumu Tanaka, Masahiko Miura, Mikihiko Kogo, Tetsuro Watabe
Organizer
AACR Virtual Special Conference: Tumor Heterogeneity: From Single Cells to Clinical Impact
Related Report
Int'l Joint Research
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[Presentation] Targeting all transforming growth factor-β isoforms with a novel Fc chimeric receptor impairs tumor growth and angiogenesis of oral squamous cell2020
Author(s)
Hitomi Takahashi, Kazuki Takahashi, Yuichi Akatsu, Katarzyna A. Podyma-Inoue, Takehisa Matsumoto, Yasuhiro Yoshimatsu, Shingo Kodama, Toshihiro Uchihashi, Daizo Koinuma, Mikako Shirouzu, Kohei Miyazono and Tetsuro Watabe
Organizer
第42回日本分子生物学会年会（MBSJ2020）
Related Report
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[Presentation] TGF-β-induced cell cycle arrest is associated with increased migration and metastasis of oral squamous carcinoma cells2019
Author(s)
Kazuki Takahashi, Katarzyna A. Inoue, Yasuhiro Yoshimatsu, Atsushi Kaida, Kei Takahashi, Shimpei Kubota, Akinari Sugauchi, Toshihiro Uchihashi, Susumu Tanaka, Mikihiko Kogo, Masahiko Miura, Kohei Miyazono, Tetsuro Watabe
Organizer
AACR-JCA Joint Conference
Related Report
Int'l Joint Research
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[Presentation] Regulatory role of transforming growth factor-β signals in the migration and cell cycle of oral squamous carcinoma cells2019
Author(s)
Kazuki Takahashi, Katarzyna A. Inoue, Yasuhiro Yoshimatsu, Atsushi Kaida, Kei Takahashi, Shimpei Kubota, Akinari Sugauchi, Toshihiro Uchihashi, Susumu Tanaka, Mikihiko Kogo, Masahiko Miura, Kohei Miyazono, Tetsuro Watabe
Organizer
Keystone Symposia; Cancer Metastasis: The role of metabolism, immunity and microenvironment
Related Report
Int'l Joint Research
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