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2019 年度 実施状況報告書

Role of the angiocrine factor Egfl7 in multiple myeloma progression and drug resistance

研究課題

研究課題/領域番号 19K08857
研究機関順天堂大学

研究代表者

ハイジッヒ ベアーテ  順天堂大学, 医学(系)研究科(研究院), 特任准教授 (30372931)

研究分担者 服部 浩一  順天堂大学, 医学(系)研究科(研究院), 特任先任准教授 (10360116)
研究期間 (年度) 2019-04-01 – 2022-03-31
キーワードmultiple myeloma / cell growth / integrin / proliferation / KLF2 / ITGB3 / adhesion / proliferation
研究実績の概要

We showed Egfl7 and Beta3 integrin expression in patient samples and cell lines . Functionally, we showed that overexpression increased, while knockdown decreased myeloma cell proliferation.
We used 2 murine models of myeloma to show that inhibition of Egfl7 using neutralizing antibodies against Egfl7 prevented myeloma growth.
Mechanistically we demonstrated that overexpression of ITGB3 or EGFL7 enhanced MM cell adhesion and proliferation. Intriguingly, ITGB3 overexpression upregulated the transcription factor Krueppel-like factor 2 (KLF2), which further enhanced EGFL7 transcription in MM cells, thereby establishing an EGFL7-ITGB3-KLF2-EGFL7 amplification loop that supports MM cell survival and proliferation.

現在までの達成度 (区分)
現在までの達成度 (区分)

2: おおむね順調に進展している

理由

no major problems experimentally (until the outbreak of the coronavirus pandemic).
Since March 2020 the research center and its facilities can not be used as frequently. We all hope research efforts around the world will help to prevent more pain and death.

今後の研究の推進方策

We are currently examining how Egfl7 can modulate other cellular functions, and are screening for other cellular receptors that might be involved multiple myeloma pathology.

We also are testing drugs that blocks those other receptors as a novel treatment option for multiple myeloma

  • 研究成果

    (2件)

すべて 2020

すべて 雑誌論文 (1件) (うち査読あり 1件、 オープンアクセス 1件) 学会発表 (1件) (うち国際学会 1件、 招待講演 1件)

  • [雑誌論文] The EGFL7-ITGB3-KLF2 axis enhances survival of multiple myeloma in preclinical models2020

    • 著者名/発表者名
      Yousef Salama, Satoshi Takahashi, Koichi Hattori and Beate Heissig.
    • 雑誌名

      Blood Ad

      巻: 4(6) ページ: 1021-1037

    • DOI

      10.1182/bloodadvances.2019001002

    • 査読あり / オープンアクセス
  • [学会発表] The Fibrinolytic System Orchestrates the Development of Inflammation and Inflammation-Associated Carcinogenesis in the Proteolytic Niche2020

    • 著者名/発表者名
      Heissig Beate
    • 学会等名
      Gordon Conference
    • 国際学会 / 招待講演

URL: 

公開日: 2021-01-27  

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