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Investigation of mechanical properties of tumor microenvironment with spatial and temporal heterogeneity of oxygen tension for control of tumor cell behavior(Fostering Joint International Research)

Research Project

Project/Area Number 16KK0138
Research Category

Fund for the Promotion of Joint International Research (Fostering Joint International Research)

Allocation TypeMulti-year Fund
Research Field Biomedical engineering/Biomaterial science and engineering
Research InstitutionTohoku University

Principal Investigator

Funamoto Kenichi  東北大学, 流体科学研究所, 准教授 (70451630)

Project Period (FY) 2017 – 2019
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥14,040,000 (Direct Cost: ¥10,800,000、Indirect Cost: ¥3,240,000)
Keywordsマイクロ・ナノデバイス / 細胞・組織 / 生物・生体工学 / 流体工学 / ナノバイオ / マイクロ流体デバイス / がん微小環境 / 低酸素
Outline of Final Research Achievements

Effects of spatiotemporal heterogeneity of oxygen concentration on mechanical properties of cancer cells and the surrounding extracellular matrix were investigated. A 3-in-1 chip which reproduces in vivo microenvironment was developed and employed to simultaneously control oxygen tension and mechanical and chemical stimuli to cells. Proliferation and migration speed of human breast cancer cell (MDA-MB-231 cell line) were increased under hypoxia than those under normoxia. However, these tendencies became unclear when the cancer cells were co-cultured with the vascular endothelial cells. Contraction and degradation of collagen gel was promoted under the co-culture condition, but its speed was slowed down by hypoxic exposure. Thus, it was found that changes of the cancer cell behaviors and the surrounding extracellular matrix as well as their interactions were oxygen-dependent.

Academic Significance and Societal Importance of the Research Achievements

がん微小環境では、細胞群の過剰な増殖により慢性的かつ不均一な低酸素状態が生成されるとともに、未成熟な血管網の形成に起因して一過性の低酸素負荷と再酸素化が生じる。本研究では、酸素濃度の変化が、がん細胞やその周囲の細胞外マトリクスの力学的特性と、それらの間の相互作用に与える影響の一端を解明した。本研究で観察された酸素濃度に依存する微小環境における現象は、がんの増殖と転移の問題に限らず、様々な疾患の予防や治療、再生医療の進展に重要な知見をもたらすものである。

Report

(2 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • Research Products

    (6 results)

All 2020 2019 2018

All Int'l Joint Research (1 results) Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (2 results) (of which Int'l Joint Research: 1 results)

  • [Int'l Joint Research] マサチューセッツ工科大学(米国)2018

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Microfluidic platform for three-dimensional cell culture under spatiotemporal heterogeneity of oxygen tension2020

    • Author(s)
      Koens Rei、Tabata Yugo、Serrano Jean C.、Aratake Satoshi、Yoshino Daisuke、Kamm Roger D.、Funamoto Kenichi
    • Journal Title

      APL Bioengineering

      Volume: 4 Issue: 1 Pages: 016106-016106

    • DOI

      10.1063/1.5127069

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 生体内低酸素微小環境を再現するマイクロ流体デバイス2020

    • Author(s)
      船本 健一
    • Journal Title

      月刊「細胞」

      Volume: 52 Pages: 50-53

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Oxygen-dependent contraction and degradation of the extracellular matrix mediated by interaction between tumor and endothelial cells2019

    • Author(s)
      Yoshino Daisuke、Funamoto Kenichi
    • Journal Title

      AIP Advances

      Volume: 9 Issue: 4 Pages: 045215-045215

    • DOI

      10.1063/1.5089772

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 酸素濃度勾配下における乳腺がん細胞の遊走2019

    • Author(s)
      船本 健一、コーエンズ 礼、田端 優吾、吉野 大輔
    • Organizer
      日本機械学会第32回バイオエンジニアリング講演会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Oxygen-dependent migration of breast cancer cell is altered by cell-cell interaction with vascular endothelial cells2019

    • Author(s)
      Kenichi Funamoto、Rei Koens、Yugo Tabata、Daisuke Yoshino
    • Organizer
      The 17th International Conference on Biomedical Engineering (ICBME 2019)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research

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Published: 2017-03-15   Modified: 2021-02-19  

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