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Can MIC-1 improve medical care for biliary tract cancer

Research Project

Project/Area Number 19K17470
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionFukushima Medical University

Principal Investigator

Sugimto Mitsuru  福島県立医科大学, 医学部, 助教 (10722473)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsMIC-1 / 胆道癌 / アポトーシス / 胆管癌
Outline of Research at the Start

胆管癌は診断時に切除不能で化学療法を行われる症例が少なくなく、適切な病勢予測マーカー、より有効な治療法が求められている。Macrophage inhibitory cytokine(MIC-1)は炎症や様々な悪性腫瘍で増加し、特に膵癌と胆管癌で高値を示すことが報告されており、我々は血清・胆汁MIC-1が早期胆管癌の診断に有用なマーカーであることを発見した。しかし、MIC-1の腫瘍に対する効果は、促進、またはアポトーシスによる抑制のいずれかで臓器ごとに異なっている。本研究では、胆管癌におけるMIC-1の効果を明らかにし、将来胆管癌の診療・治療に応用する。

Outline of Final Research Achievements

Biliary tract cancer (BTC) is a lethal disease; therefore, there is a need for useful biomarkers and treatments. The serum levels of macrophage inhibitory cytokine-1 (MIC-1), a member of the TGF-β superfamily, are elevated in pancreaticobiliary cancers. However, the effect of MIC-1 on BTC is unknown. MIC-1 expression was confirmed in BTC tissue specimens and was higher in BTC cells than in normal bile duct epithelial cells, as determined by western blotting and RT-PCR. In cell culture experiments, MIC-1 increased BTC cell proliferation and invasion by preventing apoptosis and inhibited the effect of gemcitabine. In vivo, serum MIC-1 showed a positive correlation with BTC progression and serum M30 levels. The ability to diagnose BTC at an early stage or at all stages was improved by using the combination of MIC-1 and M30. MIC-1 is a useful diagnostic and prognostic biomarker as well as a potential therapeutic target for BTC.

Academic Significance and Societal Importance of the Research Achievements

胆道癌は致死的な疾患であり、有用な診断・予後予測マーカーも存在しない。診断時には切除不能なことも多く、最も効果のみられる化学療法でも生存期間は満足のいく成績ではない。今回の研究結果からMIC-1は胆道癌の早期診断に貢献するものと考えられた。また、MIC-1は腫瘍の進行とも相関しており、予後予測マーカーとしても有用であった。MIC-1は腫瘍増殖を促進していたことからも、抗MIC-1抗体などによる胆道癌の治療の発展が期待できる。さらにMIC-1の胆道癌への作用を調べることにより、新たな診断マーカー、治療法を作り出すことができる可能性がある。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Products Report
  • Research Products

    (1 results)

All 2022

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

  • [Journal Article] Clinical usefulness and acceleratory effect of macrophage inhibitory cytokine-1 on biliary tract cancer : an experimental biomarker analysis2022

    • Author(s)
      Sugimoto, M., Suzuki, R., Nozawa, Y., Takagi, T., Konno, N., Asama, H., Sato, Y., Irie, H., Nakamura, J., Takasumi, M., Hashimoto, M., Kato, T., Kobashi, R., Suzuki, O., Hashimoto, Y., Hikichi, T., Ohira, H.
    • Journal Title

      Cancer Cell International

      Volume: 22 Issue: 1 Pages: 250-265

    • DOI

      10.1186/s12935-022-02668-x

    • Related Report
      Products Report
    • Peer Reviewed / Open Access

URL: 

Published: 2019-04-18   Modified: 2024-03-28  

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