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Exosomes promoting malignancy and affecting tumor microenvironment, the target for anti-tumor therapy.

Research Project

Project/Area Number 17K11828
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Surgical dentistry
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Inoue Katarzyna Anna  東京医科歯科大学, 大学院医歯学総合研究科, 助教 (90302877)

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.

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。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (21 results)

All 2021 2020 2019 2018 2017

All Journal Article (5 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (16 results) (of which Int'l Joint Research: 6 results,  Invited: 2 results)

  • [Journal Article] Activation of β2-adrenergic receptor signals suppresses mesenchymal phenotypes of oral squamous cell carcinoma cells.2021

    • Author(s)
      Sakakitani S, Podyma-Inoue KA, Takayama R, Takahashi K, Ishigami-Yuasa M, Kagechika H, Harada H, Watabe T.
    • Journal Title

      Cancer Sci

      Volume: 112 Issue: 1 Pages: 155-167

    • DOI

      10.1111/cas.14670

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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
    • Journal Title

      Cancer Sciense

      Volume: - Issue: 7 Pages: 2385-2399

    • DOI

      10.1111/cas.14455

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Targeting all transforming growth factor-β isoforms with an Fc chimeric receptor impairs tumor growth and angiogenesis of oral squamous cell cancer2020

    • Author(s)
      Takahashi Kazuki, Akatsu Yuichi, Podyma-Inoue Katarzyna A., Matsumoto Takehisa, Takahashi Hitomi, Yoshimatsu Yasuhiro, Koinuma Daizo, Shirouzu Mikako, Miyazono Kohei, Watabe Tetsuro
    • Journal Title

      Journal of Biological Chemistry

      Volume: 295 Issue: 36 Pages: 12559-12572

    • DOI

      10.1074/jbc.ra120.012492

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 【エクソソーム最前線】 血管とエクソソーム 炎症と免疫.2018

    • Author(s)
      井上 カタジナアンナ, 渡部 徹郎
    • Journal Title

      炎症と免疫

      Volume: 26 Pages: 280-285

    • Related Report
      2018 Research-status Report
  • [Journal Article] Regulatory role of transforming growth factor-β signals in the migration and tumor formation of HOC313-LM cells, an oral squamous cell carcinoma2018

    • Author(s)
      Kazuki Takahashi, Katarzyna A. Podyma-Inoue, Chihiro Takao, Yasuhiro Yoshimatsu Y, Tomoki Muramatsu, Johji Inazawa and Tetsuro Watabe
    • Journal Title

      Journal Stomatological Society, Jpn.

      Volume: 85 Pages: 52-61

    • NAID

      40021649452

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] TNF-αはTGF-βシグナルの増強を介してTGF-βによって誘導される血管の内皮間葉移行を促進する2020

    • Author(s)
      若林育海, 吉松康裕, 紀室志織, 高橋直也, 高橋和樹, 伊東史子, 小林美穂, 井上カタジナアンナ,宮園浩平, 渡部徹郎
    • Organizer
      第93回日本生化学会大会
    • Related Report
      2020 Annual Research Report
  • [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
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] TGF-β-induced cell cycle arrest is associated with increased migration and metastasis of oral squamous carcinoma cells2020

    • Author(s)
      Kazuki Takahashi, Katarzyna A. Inoue, Atsushi Kaida, Akinari Sugauchi, Toshihiro Uchihashi, Yasuhiro Yoshimatsu, Susumu Tanaka, Masahiko Miura, Mikihiko Kogo, Tetsuro Watabe
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] β2-アドレナリン受容体シグナルは口腔扁平癌の進行を阻害する2020

    • Author(s)
      榊谷 振太郎、井上 カタジナ アンナ、高橋 和樹、原田 浩之、渡部 徹郎
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Novel approach for treatment of oral squamous cell carcinoma2020

    • Author(s)
      Katarzyna A. Inoue, Shintaro Sakakitani, Kazuki Takahashi, Hiroyuki Harada, Tetsuro Watabe
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [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
      2020 Annual Research Report
  • [Presentation] 口腔がんの進展におけるTGF-βシグナルの役割2019

    • Author(s)
      高橋和樹、井上カタジナアンナ、 戒田篤志、 高橋恵生、 久保田晋平、 須河内 昭成、 内橋 峻大、 田中 晋、古郷 幹彦、 三浦雅彦、 宮園 浩平、 渡部 徹郎
    • Organizer
      Research PlaNet 2019
    • Related Report
      2019 Research-status Report
  • [Presentation] TGF-βにより細胞周期が停止した口腔扁平上皮がん細胞の運動能ならびに転移能は亢進する2019

    • Author(s)
      高橋和樹、 井上カタジナアンナ、 戒田篤志、 高橋恵生、 久保田晋平、 須河内昭成、 内橋俊大、 田中晋、 古郷幹彦三、 浦雅彦、 宮園浩平、 渡部徹郎
    • Organizer
      第78回日本癌学術総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Characterization of exosomes secreted from oral squamous carcinoma cells during epithelial to mesenchymal transition2019

    • Author(s)
      Katarzyna Inoue, Rina Takayama, Kazuki Takahashi and Tetsuro Watabe
    • Organizer
      The 11th International Conference on Proteoglycans
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [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
      2018 Research-status Report
    • Int'l Joint Research
  • [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
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 口腔扁平上皮がん細胞のTGF-βによる細胞周期制御と運動能亢進は関与する2018

    • Author(s)
      高橋 和樹, 井上 カタジナ アンナ, 吉松 康裕, 戒田 篤志, 三浦 雅彦, 渡部 徹郎
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Cell cycle arrest in oral squamous carcinoma cells undergoing TGF-β-induced epithelial to mesenchymal transition2017

    • Author(s)
      Katarzyna A. Inoue, Kazuki Takahashi, Takumi Matsuda, Yasuhiro Yoshimatsu, Atsushi Kaida, Masahiko Miura and Tetsuro Watabe
    • Organizer
      FASEB Conference "TGF-B Superfamily: Signaling in Development and Disease"
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Relationship between cell cycle arrest and epithelial to mesenchymal transition (EMT) induced by TGF-β in oral squamous carcinoma cell2017

    • Author(s)
      Tetsuro Watabe, Kazuki Takahashi, Takumi Matsuda, Yasuhiro Yoshimatsu, Atsushi Kaida, Masahiko Miura and Katarzyna A. Inoue
    • Organizer
      ERATO/AMED-CREST/PRESTO Joint International Symposium
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Exosomes secreted by oral squamous carcinoma cells undergoing TGF-β-induced epithelial to mesenchymal transition2017

    • Author(s)
      Katarzyna A. Inoue, Kazuki Takahashi, Takumi Matsuda, Yasuhiro Yoshimatsu, Miki Yokoyama and Tetsuro Watabe
    • Organizer
      ConBio2017
    • Related Report
      2017 Research-status Report
  • [Presentation] 口腔がん細胞のTGF-βによる上皮間葉移行に伴う細胞周期制御の検討2017

    • Author(s)
      高橋 和樹, 井上 カタジナアンナ, 吉松 康裕, 戒田 篤志, 三浦 雅彦, 渡部 徹郎
    • Organizer
      ConBio2017
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2022-01-27  

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