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Roles of Dio2 (deiodinase, iodothyronine, type II) in colorectal tumorigenesis

Research Project

Project/Area Number 17K07191
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Tumor biology
Research InstitutionAichi Cancer Center Research Institute

Principal Investigator

Kojima Yasushi  愛知県がんセンター(研究所), がん病態生理学分野, 主任研究員 (30464217)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords大腸がん / 甲状腺 / DIO2 / 大腸 / 腫瘍血管 / 遺伝子改変動物 / がん微小環境
Outline of Final Research Achievements

The prohormone thyroxine (T4) in circulation is converted to bioactive T3 in peripheral organs by the enzyme DIO2 (deiodinase, iodothyronine, type II), a major regulator of local thyroid hormone levels. Expression of Dio2 is upregulated in intestinal polyps of Apc mice, a mouse model of familial adenomatous polyposis and early-stage sporadic CRC. Treatment with iopanoic acid, a deiodinase inhibitor, or chemical thyroidectomy suppresses tumor formation in Apc mice, accompanied by reduced tumor cell proliferation and angiogenesis. The Cancer Genome Atlas (TCGA) data indicates up-regulation of DIO2 in CRC clinical samples and a close association of its expression pattern with the stromal component, consistently with almost exclusive expression of DIO2 in the stroma of human CRC as revealed by in situ hybridization. Collectively, these data highlight biological roles of DIO2 in the CRC tumor microenvironment.

Academic Significance and Societal Importance of the Research Achievements

本研究では、甲状腺ホルモンの局所組織での活性化に重要な役割を果たすDIO2が腫瘍組織の間質で高発現して、腫瘍血管増生、腫瘍成長を促進することを見出した。欧米を中心とした疫学調査では、甲状腺疾患と大腸がん発生には、なんらかの関係があることが示唆されている。しかしながら、なぜ、甲状腺と大腸がんに関連性が発生するのかについては、謎とされている。本研究の成果は、その謎の解明に資する可能性がある。また今後のより詳しい解析が必要であるが、さまざまな腫瘍組織でDIO2が腫瘍血管の増生に重要な役割を果たしている可能性がある。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (3 results)

All 2019 2018

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

  • [Journal Article] Stromal iodothyronine deiodinase 2 ( DIO 2) promotes the growth of intestinal tumors in Apc Δ716 mutant mice2019

    • Author(s)
      Kojima Yasushi、Kondo Yuriko、Fujishita Teruaki、Mishiro‐Sato Emi、Kajino‐Sakamoto Rie、Taketo Makoto Mark、Aoki Masahiro
    • Journal Title

      Cancer Science

      Volume: 110 Issue: 8 Pages: 2520-2528

    • DOI

      10.1111/cas.14100

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 腸管腫瘍形成におけるDio2(2型脱ヨード酵素)の生物学的役割2019

    • Author(s)
      小島 康
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Role of Dio2 (deiodinase, Iodothyronine, Type II) in colon tumorigenesis.2018

    • Author(s)
      Kojima, Y., Fujishita T., Mishiro E., Kajino R., Taketo, M.M. & Aoki M.
    • Organizer
      The 77th Annual Meeting of the Japanese Cancer Association, Osaka
    • Related Report
      2018 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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