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Analysis of ameloblastic carcinoma with focus on epigenomic alterations

Research Project

Project/Area Number 20K18490
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 57020:Oral pathobiological science-related
Research InstitutionFukuoka Dental College

Principal Investigator

Yoshimoto Shohei  福岡歯科大学, 口腔歯学部, 講師 (70780188)

Project Period (FY) 2020-04-01 – 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 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsエナメル上皮腫癌 / エナメル上皮腫 / エナメル上皮癌 / エピゲノム
Outline of Research at the Start

エナメル上皮癌は顎骨に発生する癌の一つです。良性のエナメル上皮腫からの再発・悪性転化が報告されていますが、発症機序には不明な点が多いです。治療には顎骨切除手術が行われますが、広範囲の切除が必要であり、かつ予後不良であるため、治療標的の検討及び悪性化の予防法・早期診断法の確立が求められています。
本研究では、病理組織標本を用いたエピゲノム変異解析と、エナメル上皮腫細胞株・組織の三次元培養に対するDNAメチル化異常誘発による癌化モデル構築によって、エナメル上皮癌発症の機序の解明を目指します。

Outline of Final Research Achievements

Ameloblastic carcinoma (AC) is a primary odontogenic carcinoma that histologically resembles Ameloblastoma (AM). Most AC arise de novo, but there may be a pre-existing AM. Clinical behavior of AC is more aggressive and invasive than that of AM. AC sometimes shows recurrence and metastasis and has a poor prognosis. However, the mechanisms of AC oncogenesis remain unclear. Thus, the discovery of useful biomarkers for AC has been strongly required not only for making a definite pathological diagnosis but also for developing a new clinical therapy for the prevention of AC. In this study, we analyzed the expression of the IDH1 gene, a regulator of DNA methylation, in AM and AC specimens. In addition, spatial transcriptome analysis was performed to comprehensively investigate the expression of related genes. In addition, we performed three-dimensional culture using AM cell line AM-1 to establish a cell experimental system that more closely resembles a living organism.

Academic Significance and Societal Importance of the Research Achievements

エナメル上皮癌は歯原性悪性腫瘍の中で最も多いとされているものの、希少癌にあたるため、不明な点が多く、癌微小環境とエピゲノム異常に着目した研究は行われていない。現在発表されている論文は、症例報告がほとんどであり、発症機序や治療標的に関する研究はほとんど進んでいない。
従って、本研究はエナメル上皮癌の発症機序解明および早期診断法、治療法の開発に繋がる可能性のある先駆的な位置づけにあると考える。本研究成果はエナメル上皮癌の診断法および治療法の開発に繋がる可能性を秘めているため、学術的にも社会的にも意義深いと考える。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (10 results)

All 2023 2022 2021 2020

All Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (4 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results)

  • [Journal Article] Establishment of a novel protocol for formalin-fixed paraffin-embedded organoids and spheroids2023

    • Author(s)
      Yoshimoto Shohei、Taguchi Masahide、Sumi Satoko、Oka Kyoko、Okamura Kazuhiko
    • Journal Title

      Biology Open

      Volume: 12 Issue: 5

    • DOI

      10.1242/bio.059882

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] IL-6 plays a critical role in stromal fibroblast RANKL induction and consequent osteoclastogenesis in ameloblastoma progression.2023

    • Author(s)
      Yoshimoto S, Morita H, Okamura K, Hiraki A, Hashimoto S.
    • Journal Title

      Laboratory Investigation

      Volume: 103 Issue: 1 Pages: 100023-100023

    • DOI

      10.1016/j.labinv.2022.100023

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] αTAT1-induced tubulin acetylation promotes ameloblastoma migration and invasion2022

    • Author(s)
      Shohei Yoshimoto, Hiromitsu Morita, Kazuhiko Okamura, Akimitsu Hiraki, Shuichi Hashimoto
    • Journal Title

      Lab Invest

      Volume: 102(1) Issue: 1 Pages: 80-89

    • DOI

      10.1038/s41374-021-00671-w

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] IDO1‐mediated Trp‐kynurenine‐AhR signal activation induces stemness and tumor dormancy in oral squamous cell carcinomas2021

    • Author(s)
      Anzai Hiromasa、Yoshimoto Shohei、Okamura Kazuhiko、Hiraki Akimitsu、Hashimoto Shuichi
    • Journal Title

      Oral Science International

      Volume: 19 Issue: 1 Pages: 31-43

    • DOI

      10.1002/osi2.1109

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] NFAT5 promotes oral squamous cell carcinoma progression in a hyperosmotic environment2020

    • Author(s)
      Yoshimoto Shohei、Morita Hiromitsu、Matsuda Miho、Katakura Yoshinori、Hirata Masato、Hashimoto Shuichi
    • Journal Title

      Laboratory Investigation

      Volume: 101 Issue: 1 Pages: 38-50

    • DOI

      10.1038/s41374-020-00486-1

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibition of Alk signaling promotes the induction of human salivary-gland-derived organoids2020

    • Author(s)
      Yoshimoto Shohei、Yoshizumi Junko、Anzai Hiromasa、Morishita Koichiro、Okamura Kazuhiko、Hiraki Akimitsu、Hashimoto Shuichi
    • Journal Title

      Disease Models & Mechanisms

      Volume: 13 Issue: 9 Pages: 1-9

    • DOI

      10.1242/dmm.045054

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Three-dimensional (3D) Experimental Models in Oral Pathology2023

    • Author(s)
      Shohei Yoshimoto
    • Organizer
      The 21st International Congress of Oral Pathology and Medicine
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 口腔腫瘍における腫瘍微小環境がその進展に与える影響の解析2022

    • Author(s)
      吉本尚平
    • Organizer
      第111回日本病理学会総会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] Hypoxia‐induced HIF‐1α and ZEB1 are critical for the malignant transformation of ameloblastoma via TGF‐β‐dependent EMT2021

    • Author(s)
      吉本尚平
    • Organizer
      第32回日本臨床口腔病理学会総会・学術大会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] HIF‐1α and ZEB1 are critical for the malignant transformation of ameloblastoma via TGF‐β‐dependent EMT2020

    • Author(s)
      吉本尚平、田中文恵、森田浩光、平木昭光、橋本修一
    • Organizer
      第109回日本病理学会総会
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2025-01-30  

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