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Functional analysis of thymosin-beta 4 in the tumor microenvironment and its applications

Research Project

Project/Area Number 21K06842
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 48040:Medical biochemistry-related
Research InstitutionWakayama Medical University

Principal Investigator

Tsuyoshi Morita  和歌山県立医科大学, 医学部, 准教授 (80403195)

Co-Investigator(Kenkyū-buntansha) 橋本 真一  和歌山県立医科大学, 先端医学研究所, 教授 (00313099)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2023: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Keywords膵癌 / 間質細胞 / がん免疫 / thymosin / 遺伝子改変マウス / がん微小環境 / thymosin-β4
Outline of Research at the Start

予後不良な癌として知られる膵癌では、しばしば強い間質反応がみられ、癌の浸潤・転移と密接に関係している。本研究で注目するthymosin-β4(Tβ4)は、癌悪性化マーカーとして良く知られる遺伝子であるが、がん微小環境における機能は全く知られていなかった。しかし、最近私が独自に作成したTβ4遺伝子改変マウスを用いて解析を行ったところ、がん微小環境の間質細胞が産生するTβ4が、癌細胞の増殖や転移に大きな影響を与えていることが示唆された。そこで本研究では、Tβ4遺伝子改変マウスを用いて、膵癌組織の微小環境におけるTβ4の役割を明らかにするとともに、Tβ4を標的とした新たな癌治療法の開発を目指す。

Outline of Final Research Achievements

To clarify the role of Tβ4 in the tumor microenvironment of pancreatic cancer, Tβ4 gene-deficient KPC mice (Tβ4-KPC mice) were obtained by crossing Tβ4 KO mice with pancreatic ductal adenocarcinoma model mice (KPC mice). Compared with KPC mice, Tβ4-KPC mice showed delayed onset and progression of pancreatic cancer. Diaphragmatic dissemination and metastasis to the liver also tended to be suppressed in Tβ4-KPC mice. In addition, RNA-seq analysis of pancreatic cancer tissues derived from these mice revealed that the expression levels of genes specific for neutrophils and B cells were significantly lower in pancreatic cancer tissues from Tβ4-KPC mice. These results suggest that Tβ4 may induce neutrophil and B cell infiltration in pancreatic cancer tissue.

Academic Significance and Societal Importance of the Research Achievements

癌細胞の増殖・転移には免疫細胞や筋線維芽細胞などの間質細胞との相互作用が重要であることが知られている。非常に予後不良な癌として知られる膵癌では、癌の進展に伴ってこれら間質細胞の浸潤や線維化などの間質反応が強く引き起こされ、これが癌の悪性度と密接に関係していることが知られている。本研究により、膵癌組織において高発現しているTβ4が、膵癌微小環境への免疫細胞の浸潤を誘導することで、癌の進展に寄与している可能性が示された。この結果により、Tβ4をターゲットとした膵癌治療法の開発が期待される。

Report

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

    (10 results)

All 2024 2023 2022 2021 Other

All Journal Article (6 results) (of which Peer Reviewed: 4 results,  Open Access: 2 results) Presentation (3 results) Remarks (1 results)

  • [Journal Article] Novel ability of diflubenzuron as an inhibitor of mitochondrial function2024

    • Author(s)
      Mori Kotaro、Nakagawa Yoshiaki、Watanabe Bunta、Miyata Hiroshi、Morita Tsuyoshi、Hayashi Ken'ichiro
    • Journal Title

      Insect Biochemistry and Molecular Biology

      Volume: 167 Pages: 104088-104088

    • DOI

      10.1016/j.ibmb.2024.104088

    • Related Report
      2023 Annual Research Report
  • [Journal Article] Role of CRP2-MRTF interaction in functions of myofibroblasts2023

    • Author(s)
      Hayashi, K., Horoiwa, S., Mori, K., Miyata, H., Labios, R.J., Morita, T., Kobayashi, Y., Yamashiro, C., Higashijima, F., Yoshimoto, T., Kimura, K., and Nakagawa
    • Journal Title

      Cell Structure and Function

      Volume: 48 Issue: 1 Pages: 83-98

    • DOI

      10.1247/csf.23004

    • ISSN
      0386-7196, 1347-3700
    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Significance of the p38MAPK-CRP2 axis in myofibroblastic phenotypic transition2023

    • Author(s)
      Hayashi Kenichiro、Labios Reuben Jacob、Morita Tsuyoshi、Ashimori Atsushige、Aoki Ren、Mikuni Masanori、Kimura Kazuhiro
    • Journal Title

      Cell Structure and Function

      Volume: 48 Issue: 2 Pages: 199-210

    • DOI

      10.1247/csf.23060

    • ISSN
      0386-7196, 1347-3700
    • Related Report
      2023 Annual Research Report
  • [Journal Article] Actin‐related protein 5 suppresses the cooperative activation of cardiac gene transcription by myocardin and MEF22023

    • Author(s)
      Morita Tsuyoshi、Hayashi Ken'ichiro
    • Journal Title

      FEBS Open Bio

      Volume: 13 Issue: 2 Pages: 363-379

    • DOI

      10.1002/2211-5463.13549

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulation of Arp5 expression by alternative splicing coupled to nonsense-mediated RNA decay2023

    • Author(s)
      Morita Tsuyoshi、Hayashi Ken'ichiro
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 657 Pages: 50-58

    • DOI

      10.1016/j.bbrc.2023.03.047

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Actin-related protein 5 functions as a novel modulator of MyoD and MyoG in skeletal muscle and in rhabdomyosarcoma2022

    • Author(s)
      Morita Tsuyoshi、Hayashi Ken'ichiro
    • Journal Title

      eLife

      Volume: 11

    • DOI

      10.7554/elife.77746

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] ARP5はMYOCDとMEF2による心筋遺伝子発現の協調的活性化を抑制する2023

    • Author(s)
      森田強、林謙一郎
    • Organizer
      第96回日本生化学会大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 横紋筋肉腫におけるApr5によるmyogenic regulatory factorの活性抑制機構の解明2022

    • Author(s)
      森田強、林謙一郎
    • Organizer
      第95回日本生化学会大会
    • Related Report
      2022 Research-status Report
  • [Presentation] Arp5によるMyoD/MyoG機能抑制を介した 骨格筋分化の制御機構2021

    • Author(s)
      森田強
    • Organizer
      第94回日本生化学会大会
    • Related Report
      2021 Research-status Report
  • [Remarks]

    • URL

      https://www.wakayama-med.ac.jp/med/lasbiology1/morita/research.html

    • Related Report
      2022 Research-status Report

URL: 

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

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