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Development of Simulation System of Cancer Metabolism

Research Project

Project/Area Number 17K19012
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Chemical engineering and related fields
Research InstitutionOsaka University

Principal Investigator

SHIMIZU Hiroshi  大阪大学, 情報科学研究科, 教授 (00226250)

Co-Investigator(Kenkyū-buntansha) 松田 史生  大阪大学, 情報科学研究科, 教授 (50462734)
戸谷 吉博  大阪大学, 情報科学研究科, 准教授 (70582162)
Research Collaborator Takahashi Chihiro  
Project Period (FY) 2017-06-30 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywordsがん細胞 / シミュレーション / 代謝フラックス解析 / 生物情報工学 / 代謝解析 / 代謝フラックス
Outline of Final Research Achievements

It is well known that cancer cells uptake a lot of carbon source and show the particular metabolic state called as Warburg effect metabolism. Genetic mutations related to central carbon metabolism trigger accumulation of specific metabolites and it might be related to the cancer malignant. In this study, to elucidate the state of metabolism in cancer cells 13C-metabolic flux analysis (13C-MFA) was performed with 13C-labelled compounds ([1-13C]glucose and [U-13C]glutamine). Metabolic flux distribution in the central metabolism of breast cancer (MCF-7) cells was determined by 13C-MFA with gas chromatography-mass spectrometry (GC-MS) analysis of mass isotopomer distributions (MIDs). Genome wide simulation system was also performed to predict the metabolic fluxes in the cancer cells. Flux balance analysis (FBA) method was successfully applied to genome scale metabolic model.

Academic Significance and Societal Importance of the Research Achievements

がん研究は特定の遺伝子の変異が引き金になって起こるため、従来、遺伝子変異とシグナル伝達のかく乱によって多くの研究が行われてきた。近年、遺伝子の変異に伴う代謝の変化とがんの悪性化などの研究がすすめられ注目を集めている。本研究では、代謝状態をとらえるためフラックス解析手法の開発と環境が変化した際にどのような代謝状態を取るのかといった議論を可能とするための予測システムの開発を試みた。実験的な代謝フラックス解析においてはヒト乳がん細胞の代謝状態をとらえるのに成功し、他のがん種の細胞にも適用された。またシミュレーションと実験を突き合わせることでがん細胞のシミュレーションを行う足掛かりを得ることができた。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (5 results)

All 2018 Other

All Journal Article (1 results) (of which Open Access: 1 results) Presentation (2 results) (of which Int'l Joint Research: 1 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Mass Spectrometry-Based Method to Study Inhibitor-Induced Metabolic Redirection in the Central Metabolism of Cancer Cells2018

    • Author(s)
      Araki Chie、Okahashi Nobuyuki、Maeda Kousuke、Shimizu Hiroshi、Matsuda Fumio
    • Journal Title

      Mass Spectrometry

      Volume: 7 Issue: 1 Pages: A0067-A0067

    • DOI

      10.5702/massspectrometry.A0067

    • NAID

      130007396785

    • ISSN
      2186-5116, 2187-137X
    • Year and Date
      2018-06-14
    • Related Report
      2018 Annual Research Report
    • Open Access
  • [Presentation] 13C-Metabolic flux analysis of the central carbon metabolism in three cancer cell lines2018

    • Author(s)
      Uehara Hikaru,、Araki Chie、Maeda Kousuke、Okahashi Nobuyuki、Matsuda Fumio、Shimizu Hiroshi
    • Organizer
      YABEC2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] がん種の異なる細胞間での中心代謝における13C代謝フラックス解析2018

    • Author(s)
      上原ひかる、荒木千絵、前田昂亮 、岡橋伸幸、松田史生、高橋智聡、清水浩
    • Organizer
      第70回日本生物工学会大会
    • Related Report
      2018 Annual Research Report
  • [Book] 代謝センシング -健康,食,美容,薬,そして脳の代謝を知る- 第25章 動物培養細胞の13C代謝フラックス解析2018

    • Author(s)
      岡橋伸幸、松田史生、清水浩
    • Publisher
      シーエムシー出版
    • ISBN
      9784781313504
    • Related Report
      2018 Annual Research Report
  • [Remarks] 清水浩研究室

    • URL

      http://www-shimizu.ist.osaka-u.ac.jp/hp/index.html

    • Related Report
      2018 Annual Research Report 2017 Research-status Report

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Published: 2017-07-21   Modified: 2020-03-30  

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