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Elucidation of the molecular mechanisms underlying mesenchymal transition of glioma cells using methylation array analysis

Research Project

Project/Area Number 19H03773
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 56010:Neurosurgery-related
Research InstitutionUniversity of Miyazaki

Principal Investigator

Takeshima Hideo  宮崎大学, 医学部, 教授 (70244134)

Co-Investigator(Kenkyū-buntansha) 横上 聖貴  宮崎大学, 医学部, 准教授 (40284856)
山下 真治  宮崎大学, 医学部, 助教 (40468046)
渡邉 孝  宮崎大学, 医学部, 講師 (90573337)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2021: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2020: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000)
Keywords膠肉腫 / 間葉型形質転換 / DNAメチル化アレイ解析 / Classifier / CRC culture / 上皮間葉転換
Outline of Research at the Start

悪性脳腫瘍に対する血管新生阻害薬の抵抗性の機序の1つとして、我々は腫瘍血管の増生に腫瘍細胞の上皮間葉転換(mesenchymal transition)が関与することを報告した。さらにこの現象は良性の毛様細胞性星細胞腫においても確認した。本研究では血管新生阻害薬の効果をより高めるため、その機序を解明するべくDNAメチル化アレイを用いエピジェネティックな変化に焦点を当て、網羅的な解析を行う。

Outline of Final Research Achievements

To elucidate the molecular mechanism underlying mesenchymal transition of glioma cells, we focused on the epigenetic change in glioma cells. We investigated gliosarcoma, since this tumor consists of epithelial components and mesenchymal components which share the same genetic alteration in the mosaic fashion. In this project, we analyzed using methylation EPIC BeadChip and Heidelberg CNS Tumor Classifier to compare both epigenetic pattern. However, we could not find any significant difference in epigenetic changes between both two components, suggesting that there might be alternative mechanism in mesenchymal transition of glioma cells.

Academic Significance and Societal Importance of the Research Achievements

神経膠腫の治療抵抗性の機序の1つとしてグリオーマ幹細胞の上皮間葉転換が知られているが、今回の研究のネガティブデータによりDNAのメチル化を介したエピジェネティックなメカニズムは関与が薄い可能性が示唆された。これをもとに,今後の研究の方向性が、腫瘍における微小環境における細胞間の相互作用やマイクロRNAの発現解析など、その他の調節系に焦点を絞るべき方向性が示唆されたものと考えられた。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (3 results)

All 2021 2019

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

  • [Journal Article] Detection of the KIAA1549-BRAF fusion gene in cells forming microvascular proliferations in pilocytic astrocytoma2019

    • Author(s)
      Yamashita Shinji、Takeshima Hideo、Matsumoto Fumitaka、Yamasaki Kouji、Fukushima Tsuyoshi、Sakoda Hideyuki、Nakazato Masamitsu、Saito Kiyotaka、Mizuguchi Asako、Watanabe Takashi、Ohta Hajime、Yokogami Kiyotaka
    • Journal Title

      PLOS ONE

      Volume: 14 Issue: 7 Pages: 1-13

    • DOI

      10.1371/journal.pone.0220146

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] メチオニン代謝がglioma initiating cell(GIC)に及ぼす影響の解明2021

    • Author(s)
      横上聖貴、渡邉孝、武石剛、山下真治、中武康隆、竹島秀雄
    • Organizer
      第39回日本脳腫瘍病理学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] メチオニン代謝がglioma initiating cell(GIC)に及ぼす影響の解明2021

    • Author(s)
      横上聖貴、渡邉孝、武石剛、山下真治、中武康隆、竹島秀雄
    • Organizer
      日本脳神経外科学会第80回学術総会
    • Related Report
      2021 Annual Research Report

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Published: 2019-04-18   Modified: 2023-01-30  

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