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Directional migration of cancer cells under metabolic gradients

Research Project

Project/Area Number 17K07173
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Tumor biology
Research InstitutionSaga University

Principal Investigator

Takahashi Eiji  佐賀大学, 理工学部, 教授 (30206792)

Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsがん / 血行性遠隔転移 / 酸素濃度勾配 / pH勾配 / 細胞遊走 / 方向性遊走 / イメージング / 遠隔転移 / 微小流体素子 / シミュレーション / がん微小環境 / MDA-MB-231 / マイクロフルイディクス / がん転移 / 低酸素微小環境
Outline of Final Research Achievements

We defined an extracellular metabolic cue that directs cancer cell migration. First, we devised a novel microfluidic device (GCG) that establishes gradients of pH and O2 concentration in the extracellular medium in standard culture dish. We demonstrated that MDA-MB-231 cells under GCG migrate toward higher pH/O2 regions, whereas directional migration was abolished when extracellular pH gradients were eliminated by hepes buffer. Extracellular pH in the bulk medium significantly affected directional migration. In contrast, extracellular O2 concentration gradients did not appear to guide the cells. Finally, we have proposed a model for directional cell migration under macroscopic spatial gradients in extracellular pH.

Academic Significance and Societal Importance of the Research Achievements

がんは日本人の死因の第1位を占めるが、その90%は原発がんではなく、転移したがんによるものであることから、がん転移のコントロールは極めて重要である。われわれは、がん生物学の観点から、血行性遠隔転移の最初のステップ、すなわちがん細胞が局所組織内を浸潤し腫瘍内微小血管に到達するプロセスで、固形がん組織に特有な極めて急峻な組織内代謝物質濃度勾配、とりわけpH勾配が、がん細胞遊走の方向を決め、がん細胞を血管に誘導する因子である可能性をin vitroで示した。この結果は、薬物等により組織内pHを制御することで血行性遠隔転移の確率を低下させ得る可能性を示すものである。

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

    (44 results)

All 2021 2020 2019 2018 2017 Other

All Journal Article (8 results) (of which Peer Reviewed: 7 results,  Open Access: 1 results) Presentation (33 results) (of which Int'l Joint Research: 8 results,  Invited: 6 results) Remarks (3 results)

  • [Journal Article] A Relatively Small Gradient of Extracellular pH Directs Migration of MDA-MB-231 Cells In Vitro2020

    • Author(s)
      Takahashi Eiji、Yamaguchi Daisuke、Yamaoka Yoshihisa
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 7 Pages: 2565-2565

    • DOI

      10.3390/ijms21072565

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A compact scanning probe for photoacoustic microscopy using ultrasonic actuator stage2020

    • Author(s)
      Yamaoka Y、Funatsu K、Yoshidumi Y、Kubo A、Notsuka Y、Takahashi E
    • Journal Title

      Japanese Journal of Applied Physics

      Volume: 59 Issue: 3 Pages: 030906-030906

    • DOI

      10.35848/1347-4065/ab7061

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] In vivo visualization of blood vessels in mouse ear by photoacoustic microscopy with transmissive liquid-crystal adaptive optics2020

    • Author(s)
      Notsuka Y、Kurihara M、Hashimoto N、Takahashi E、Yamaoka Y
    • Journal Title

      Proc. SPIE 11240, Photons Plus Ultrasound: Imaging and Sensing 2020

      Volume: - Pages: 1124039-1124039

    • DOI

      10.1117/12.2545777

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] An in vitro model for determining tumor cell migration under metabolic gradients2018

    • Author(s)
      Tsuruno Y, Okubo K, Fujiwara T, Yamaoka Y, Takahashi E
    • Journal Title

      Adv Exp Med Biol

      Volume: 1072 Pages: 201-205

    • DOI

      10.1007/978-3-319-91287-5_32

    • ISBN
      9783319912851, 9783319912875
    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] An in vitro model for determining tumor cell migration under metabolic gradients2018

    • Author(s)
      Tsuruno Y, Okubo K, Fujiwara T, Yamaoka Y, Takahashi E
    • Journal Title

      Adv Exp Med Biol (掲載決定)

      Volume: -

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Ru錯体による培養細胞組織中の酸素濃度勾配イメージング法の検討2018

    • Author(s)
      大久保魁馬、靏野雄介、藤原隆祐、井上海大、山岡禎久、高橋英嗣
    • Journal Title

      信学技法

      Volume: MBE2017-75 Pages: 47-52

    • Related Report
      2017 Research-status Report
  • [Journal Article] Simple and inexpensive technique for measuring oxygen consumption rate in adherent cultured cells2017

    • Author(s)
      Takahashi E, Yamaoka Y
    • Journal Title

      J Physiol Sci

      Volume: 67 Issue: 6 Pages: 731-737

    • DOI

      10.1007/s12576-017-0563-7

    • NAID

      40021363530

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Directional migration of MDA-MB-231 cells under O2/pH gradients2017

    • Author(s)
      Enokida Y, Tsuruno Y, Okubo K, Yamaoka Y, Takahashi E
    • Journal Title

      Adv Exp Med Biol

      Volume: 977 Pages: 169-174

    • DOI

      10.1007/978-3-319-55231-6_23

    • ISBN
      9783319552293, 9783319552316
    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] 透過型液晶補償光学素子を用いたin vivo高NA光音響顕微鏡の空間分解能向上2021

    • Author(s)
      能塚雄介,栗原 誠,橋本信幸,高橋英嗣,山岡禎久
    • Organizer
      レーザー学会学術講演会第41回年次大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 血管走行可視化を目指した波形相互相関光音響イメージング2021

    • Author(s)
      井上翔太,能塚雄介,高橋英嗣,山岡禎久
    • Organizer
      レーザー学会学術講演会第41回年次大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] がん細胞の方向性遊走:細胞外pH勾配と細胞内pHおよび細胞分極の関係2021

    • Author(s)
      小島健太郎、山口大輔、波田悠暉、河村勇輝、山岡禎久、高橋英嗣
    • Organizer
      2021年日本生体医工学会九州支部学術講演会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 酸素濃度およびpH勾配下のMDA-MB-231細胞の方向性遊走2021

    • Author(s)
      波田悠暉、小島健太郎、山口大輔、河村勇輝、高橋英嗣
    • Organizer
      2021年日本生体医工学会九州支部学術講演会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 2光子光音響波選択検出のための信号差分抽出法の検証2021

    • Author(s)
      金子昂司,前原正司,浜野修次郎,高橋英嗣,山岡禎久
    • Organizer
      第68回応用物理学会春季学術講演会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 円偏光ビームを用いた光音響イメージング装置の開発2021

    • Author(s)
      濱野 純,能塚雄介,高橋英嗣,山岡禎久
    • Organizer
      第68回応用物理学会春季学術講演会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Further evidence that gradients of extracellular pH direct migration of MDA-MB-231 cells in vitro.2021

    • Author(s)
      Eiji Takahashi, Yuki Hada, Daisuke Kojima, Yoshihisa Yamaoka
    • Organizer
      ISOTT2021
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 細胞外pHがMDA-MB-231細胞の方向性遊走にあたえる影響2020

    • Author(s)
      山口大輔, 小島健太郎, 波田悠暉, 河村勇輝, 山岡禎久, 高橋英嗣
    • Organizer
      生体医工学シンポジウム2020
    • Related Report
      2020 Annual Research Report
  • [Presentation] 超音波アクチュエータステージを用いた光音響顕微鏡システムの構築および性能評価2020

    • Author(s)
      吉積雄太,能塚雄介,高橋英嗣,山岡禎久
    • Organizer
      光・量子デバイス研究会「バイオメディカルフォトニクス応用」
    • Related Report
      2020 Annual Research Report
  • [Presentation] がん細胞株における酸素を必要としないミトコンドリア膜電位形成2020

    • Author(s)
      川野梨玖、高橋英嗣
    • Organizer
      第24回酸素ダイナミクス研究会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 酸素および H+濃度勾配下のMDA-MB-231 細胞の方向性遊走2020

    • Author(s)
      波田悠暉, 高橋英嗣
    • Organizer
      第71回 西日本生理学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] pH勾配下のがん細胞の方向性遊走:コンピュータシミュレーション2020

    • Author(s)
      井上海大, 小島健太郎, 山口大輔, 波田悠暉, 大庭未那, 山岡禎久, 高橋英嗣
    • Organizer
      2020年 日本生体医工学会九州支部学術講演会
    • Related Report
      2019 Research-status Report
  • [Presentation] pH勾配下のがん細胞の方向性遊走2020

    • Author(s)
      山口大輔, 井上海大, 小島健太郎, 波田悠暉, 大庭未那, 山岡禎久, 高橋英嗣
    • Organizer
      2020年 日本生体医工学会九州支部学術講演会
    • Related Report
      2019 Research-status Report
  • [Presentation] pH勾配下のがん細胞の方向性遊走:細胞内pH勾配の関与について2020

    • Author(s)
      小島健太郎、山口大輔、波田悠暉、大庭未那、井上海大、山岡禎久、髙橋英嗣
    • Organizer
      2020年 日本生体医工学会九州支部学術講演会
    • Related Report
      2019 Research-status Report
  • [Presentation] How we survive in oxygen deprivations; cellular and molecular strategies2020

    • Author(s)
      Takahashi E
    • Organizer
      The 10th Joint Seminar between Saga University and Liaoning University -New Trends in Chemistry and Materials Science-
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] In vivo visualization of blood vessels in mouse ear by photoacoustic microscopy with transmissive liquid-crystal adaptive optics2020

    • Author(s)
      Notsuka Y, Kurihara M, Hashimoto N, Takahashi E, Yamaoka Y
    • Organizer
      SPIE PHOTONICS BIOS 2020
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Photoacoustic microscopy by spatial overlap modulation using femtosecond optical pulse train2020

    • Author(s)
      Yamaoka Y, Matsumoto K, Notsuka Y, Takahashi E
    • Organizer
      SPIE PHOTONICS BIOS 2020
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 光音響イメージングのためのパルス駆動 LED 励起光源の試作2020

    • Author(s)
      東 祐希、能塚雄介、高橋英嗣、山岡禎久
    • Organizer
      2019年度応用物理学会九州支部学術講演会
    • Related Report
      2019 Research-status Report
  • [Presentation] 超音波アクチュエータステージを用いた光音響顕微鏡の小型化2020

    • Author(s)
      山岡禎久, 船津海斗, 能塚雄介, 高橋英嗣
    • Organizer
      第58回日本生体医工学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Extracellular gradients of pH direct migration of MDA-MB-231 cells2019

    • Author(s)
      Yamaguchi D, Kojima K, Yamaoka Y, Takahashi E
    • Organizer
      ISOTT2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Mitochondrial membrane potential can be sustained without functioning complex IV2019

    • Author(s)
      Takahashi E, Yamaoka Y
    • Organizer
      ISOTT2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 細胞外pH勾配による細胞遊走方向の制御2019

    • Author(s)
      山口大輔, 小島健太郎, 波田悠暉, 井上海大, 大場未那, 山岡禎久, 高橋英嗣
    • Organizer
      生体医工学シンポジウム 2019
    • Related Report
      2019 Research-status Report
  • [Presentation] pH勾配下にある腫瘍細胞の方向性遊走2019

    • Author(s)
      藤原隆祐、高橋英嗣
    • Organizer
      2019年 日本生体医工学会九州支部学術講演会
    • Related Report
      2019 Research-status Report
  • [Presentation] pH勾配下にある腫瘍細胞の方向性遊走2019

    • Author(s)
      藤原隆祐, 高橋英嗣
    • Organizer
      日本生体医工学会九州支部学術講演会
    • Related Report
      2018 Research-status Report
  • [Presentation] 教育講演:細胞・臓器・生体における酸素の測定2018

    • Author(s)
      高橋英嗣
    • Organizer
      第22回酸素ダイナミクス研究会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 代謝リプログラミングにおけるミトコンドリア膜電位の維持2018

    • Author(s)
      高橋英嗣
    • Organizer
      第69回西日本生理学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Ru錯体による培養細胞組織中の酸素濃度勾配イメージング法の検討2018

    • Author(s)
      大久保魁馬、靏野雄介、藤原隆祐、井上海大、山岡禎久、高橋英嗣
    • Organizer
      MEとバイオサイバネティックス研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] 生体組織における酸素測定とその課題2018

    • Author(s)
      高橋英嗣
    • Organizer
      日本大学工学部酒谷研究室セミナー
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] An in vitro model for determining tumor cell migration under metabolic gradients2017

    • Author(s)
      Tsuruno Y, Okubo K, Fujiwara T, Yamaoka Y, Takahashi E
    • Organizer
      ISOTT2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 培養細胞培地に形成されるO2勾配のイメージング2017

    • Author(s)
      大久保魁馬、靏野雄介、藤原隆祐、榎田祐也、山岡禎久、高橋英嗣
    • Organizer
      日本生体医工学会九州支部学術講演会
    • Related Report
      2017 Research-status Report
  • [Presentation] Anoxic core in single cardiac myocyte: how the cell survives in hypoxia2017

    • Author(s)
      Takahashi E
    • Organizer
      群馬大学理工学府分子科学部門大学院セミナー
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] MDA-MB-231細胞の遊走方向を決める細胞外因子2017

    • Author(s)
      藤原隆祐, 大久保魁馬, 靏野雄介, 井上海大, 山岡禎久,高橋英嗣
    • Organizer
      第21回酸素ダイナミクス研究会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Life with less oxygen: how mitochondria sustain membrane potential in metabolic reprogramming2017

    • Author(s)
      Takahashi E
    • Organizer
      UCC, School of Biochemistry and Cell Biology Seminar
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Remarks] ATF: BIOMED ENG TAKAHASHI LAB

    • URL

      http://www.ee.saga-u.ac.jp/sensor/ATF_Biomed/Research.html

    • Related Report
      2018 Research-status Report
  • [Remarks] RESEARCH

    • URL

      http://www.ee.saga-u.ac.jp/sensor/ATF_Biomed/Research.html

    • Related Report
      2017 Research-status Report
  • [Remarks] RESEARCH

    • URL

      http://www.ee.saga-u.ac.jp/sensor/ATF_Biomed_J/Research.html

    • Related Report
      2017 Research-status Report

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

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