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主発性および転移性大腸がんにおけるLgr5+幹細胞の明確な役割
Felipe de Sousa e Melo1, Antonina V Kurtova1, Jonathan M Harnoss2
1Molecular Oncology, Genentech, 1 DNA Way, South San Francisco, California 94080, USA.
Nature
|March 31, 2017
まとめ
ガン幹細胞 (CSC) は腫瘍の成長と転移を促します Lgr5+ CSCを標的にすることは,Lgr5-細胞が補償し,原発性対転移性大腸がんにおける異なるCSCの役割を強調するので,原発性腫瘍を抑制しますが,それらを治すことはできません.
科学分野:
- 腫瘍学
- 胃腸内科
- 細胞生物学
背景:
- ガン幹細胞 (CSC) は腫瘍の進行と転移に関与しています.
- ほとんどのがんにおけるその機能的関連性は,実験的に確認されていない.
- 特定のCSCマーカーを特定することは,標的型がん治療において極めて重要です.
研究 の 目的:
- 腸がん幹細胞 (CSC) の識別と標的化におけるレウシンに富んだGタンパク質結合受容体5 (Lgr5) の役割を調査する.
- 主要腫瘍の成長と大腸がんの転移におけるLgr5+ CSCの機能的関連性を決定する.
- 転移性疾患の管理のためにCSCを標的とした治療戦略を探求する.
主な方法:
- 人間の結腸直腸がんの進行を再現したマウスモデル.
- Lgr5 を発現する細胞 (Lgr5+) を選択的に除去する.
- 主要腫瘍の成長,回帰,転移の可能性の分析.
主要な成果:
- Lgr5は,設計された大腸がんモデルにおける腸内CSCを識別する.
- 選択的なLgr5+細胞除去は,原発腫瘍の成長を制限したが,後退を引き起こさなかった.
- Lgr5- 細胞はLgr5+ CSCのプールを補充し,治療終了後に腫瘍の再発を引き起こした.
- CSCは肝臓転移の形成と維持に不可欠でした.
結論:
- 原発性対転移性腫瘍の成長には明確なCSC依存関係がある.
- Lgr5+ CSCを標的にすることは,転移性大腸がんの管理のための治療戦略である可能性があります.
- Lgr5-細胞はLgr5+CSCの損失を補うことができるので,併用療法が必要になる可能性がある.
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