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Elucidating the role of iron in tumor microenvironment

Research Project

Project/Area Number 21H02764
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 50010:Tumor biology-related
Research InstitutionKumamoto University

Principal Investigator

Moroishi Toshiro  熊本大学, 大学院生命科学研究部(医), 教授 (30647722)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2023: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2022: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2021: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Keywords鉄代謝 / がん / 免疫 / 腫瘍微小環境 / 炎症 / 代謝競合 / シグナル / 免疫応答
Outline of Research at the Start

近年、腫瘍微小環境において、がん細胞や免疫細胞など多細胞間での代謝の競合が腫瘍運命を決定する重要な要素の一つであることが明らかになりつつある。鉄は生体に必須の栄養素であり様々な生命機能を制御するが、腫瘍微小環境における鉄の役割は十分に解明されていない。本研究では腫瘍微小環境に存在する様々な細胞で鉄代謝を変容させることで、腫瘍運命の決定における鉄代謝の役割を調べる。本研究の遂行により鉄が制御する新たな生命機能や病態を明らかにするとともに、鉄動態の変容によるがんや炎症性疾患等の新たな予防・治療法の創薬シーズ開発を目指す。

Outline of Final Research Achievements

Cancer cells, along with immune cells and stromal cells interspersed around them, form a complex cellular community known as the tumor microenvironment. Within this tumor microenvironment, various cells interact and play roles in cancer progression. Recently, changes in metabolism among cells within this tumor microenvironment have been recognized as important factors influencing cancer progression. While iron is an essential nutrient in living organisms, controlling various life functions, its role in the tumor microenvironment remains poorly understood. In this research project, we investigated the importance of iron in various cells present in the tumor microenvironment. As a result, we found that iron in the tumor microenvironment influences the growth of cancer cells and immune responses.

Academic Significance and Societal Importance of the Research Achievements

鉄は生体に必須の栄養素であり、軽度の不足は貧血を引き起こし、重度の不足では生命活動を維持できなくなる。一方、その過剰は神経変性疾患やがんに関連することも知られており、生体において鉄量のバランスを維持することは非常に重要である。本研究ではがん細胞の成長や免疫応答における鉄バランスの重要性を明らかにした。これらの研究成果は、鉄が腫瘍微小環境においてがん細胞や免疫細胞にどのように影響を与え、がんの進展にどう寄与していくかという学術的理解を深めるだけでなく、今回解明された分子機構を基盤に将来的な研究を発展させることで、がんに対する新たな治療法開発への一助となることも期待される。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • Research Products

    (16 results)

All 2023 2022 2021 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (12 results) (of which Int'l Joint Research: 3 results,  Invited: 4 results) Remarks (2 results)

  • [Journal Article] Distinct functions between ferrous and ferric iron in lung cancer cell growth2023

    • Author(s)
      Hinokuma Hironori、Kanamori Yohei、Ikeda Koei、Hao Li、Maruno Masataka、Yamane Taishi、Maeda Ayato、Nita Akihiro、Shimoda Mayuko、Niimura Mayumi、Takeshima Yuki、Li Shuran、Suzuki Makoto、Moroishi Toshiro
    • Journal Title

      Cancer Science

      Volume: 114 Issue: 11 Pages: 4355-4364

    • DOI

      10.1111/cas.15949

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Iron accelerates Fusobacterium nucleatum-induced CCL8 expression in macrophages and is associated with colorectal cancer progression.2022

    • Author(s)
      Yamane T, Kanamori Y, Sawayama H, Yano H, Nita A, Ohta Y, Hinokuma H, Maeda A, Iwai A, Matsumoto T, Shimoda M, Niimura M, Usuki S, Yasuda-Yoshihara N, Niwa M, Baba Y, Ishimoto T, Komohara Y, Sawa T, Hirayama T, Baba H, Moroishi T.
    • Journal Title

      JCI Insight.

      Volume: 7(21) Issue: 21 Pages: 156802-156802

    • DOI

      10.1172/jci.insight.156802

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Dysfunction of FBXL5-mediated ferrous iron homeostasis suppresses lung cancer growth2023

    • Author(s)
      Hironori Hinokuma, Yohei Kanamori, Koei Ikeda, Hirokazu Hamasaki, Chika Shirakami, Eri Matsubara, Yoshinobu Osumi, Kosuke Fujino, Toshiro Moroishi, Makoto Suzuki
    • Organizer
      2023 World Conference on Lung Cancer
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Intracellular ferritin expression levels regulate growth and resistance to ferroptosis in pancreatic cancer cell lines2023

    • Author(s)
      Masataka Maruno, Yo-hei Kanamori, Takashi Matsumoto, Yuta Shiraishi, Toru Takematsu, Tatsunori Miyata, Kosuke Mima, Shigeki Nakagawa, Hidetoshi Nitta, Hiromitsu Hayashi, Toshiro Moroishi, Hideo Baba
    • Organizer
      AACR Annual Meeting 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 腫瘍微小環境におけるフェロフェイト2023

    • Author(s)
      諸石寿朗
    • Organizer
      第96回日本生化学会大会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Hippo pathway controls ferroptosis sensitivity2022

    • Author(s)
      Hao Li, Yohei Kanamori, Toshiro Moroishi
    • Organizer
      Cold Spring Harbor Asia: Iron, Reactive Oxygen Species & Ferroptosis in Life, Death & Disease
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The effect of iron metabolism on antibody production of B cell2022

    • Author(s)
      Mayuko Shimoda, Mayumi Niimura, Yuki Takeshima, Chanida Thinyakul, Narumi Harada, Saisai Liu, Toshiro Moroishi
    • Organizer
      第51回日本免疫学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 生命システムの理解を深める鉄レポーターシステムの開発2022

    • Author(s)
      前田 英仁、仁田 暁大、諸石 寿朗
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 細胞の運命決定における鉄動態の役割2022

    • Author(s)
      諸石 寿朗
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 鉄代謝の変容と細胞・組織への影響2022

    • Author(s)
      諸石 寿朗
    • Organizer
      BPCNPNPPP4学会合同年会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 傷害肝の修復に肝鉄動態が果たす意義2022

    • Author(s)
      金森耀平、諸石寿朗
    • Organizer
      第33回日本微量元素学会学術集会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 細胞内シグナルを介した鉄代謝調節因子FBXL5のリン酸化2021

    • Author(s)
      前田英仁; 諸石寿朗
    • Organizer
      第73回日本細胞生物学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] The relationship between Fusobacterium nucleatum and iron in colorectal cancer2021

    • Author(s)
      Taishi Yamane, Hiroshi Sawayama, Kosuke Mima, Masaaki Iwatsuki, Yoshifumi Baba, Takatusgu Ishimoto, Shiro Iwagami, Yuji Miyamoto, Naoya Yoshida, Toshiro Moroishi, Hideo Baba
    • Organizer
      第80回日本癌学会学術総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 大腸癌微小環境におけるFusobacterium nucleatumと鉄の関係2021

    • Author(s)
      山根大侍; 金森耀平; 江藤弘二郎; 原田和人; 澤山浩; 岩槻政晃; 岩上志朗; 馬場祥史; 宮本裕士; 吉田直矢; 諸石寿朗; 馬場秀夫
    • Organizer
      第32回日本消化器癌発生学会総会
    • Related Report
      2021 Annual Research Report
  • [Remarks] 熊本大学 大学院生命科学研究部 分子薬理学講座

    • URL

      https://www.moroishi-lab.com

    • Related Report
      2022 Annual Research Report
  • [Remarks] 熊本大学 大学院生命科学研究部 シグナル・代謝医学講座

    • URL

      https://www.moroishi-lab.com

    • Related Report
      2021 Annual Research Report

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Published: 2021-04-28   Modified: 2025-01-30  

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