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変異したクローンは正常な上皮に競争して,新たな腫瘍を排除します
B Colom1, A Herms1, M W J Hall1,2
1Wellcome Sanger Institute, Hinxton, UK.
Nature
|October 14, 2021
まとめ
早期の食道腫瘍は 通常は正常で変異した細胞との競争によって 排除されます この細胞の競争は 自然の防御機能として 腫瘍を排除し 組織の健康を維持します
科学分野:
- 発達生物学
- 癌 研究
- 細胞生物学
背景:
- 人間の上皮組織には 年齢に関係する癌誘発性突然変異が蓄積されますが 腫瘍の形成は稀です
- 変異したクローンは 普通の組織の中で 空間と生存を競い 組織動態に影響を与えます
- 早期の腫瘍形成におけるこのクローン競争の役割はほとんど不明である.
研究 の 目的:
- 正常な表皮におけるクローン競争が 初期段階の腫瘍の運命をどのように影響するかを調査する.
- 新生腫瘍の生存と除去に対する競争的相互作用の影響を決定する.
主な方法:
- 顕微鏡の腫瘍を 追跡するために 食道がんのマウスモデルを使用しました
- 長期間にわたって生き残った腫瘍の遺伝的選択を分析するために ディープシーケンシングを用いた.
- トランスジェニックのマウスを使って 複製競争を操作し 薬学的な抑制を行いました
主要な成果:
- 新しく形成された食道腫瘍のほとんどは,隣接する正常な変異クローンとの競争によって除去されました.
- 細胞死,増殖の減少,免疫反応の証拠なしに腫瘍の減少が起こりました.
- クローン競争の増加は腫瘍の早期除去を助長し,競争の抑制は腫瘍の損失を減少させた.
結論:
- 早期の腫瘍の生存は 周囲の変異クローンに対する 競争力に依存しています
- 正常な表皮の変異性クローンは 早期の腫瘍を浄化することで 予期せぬ抗腫瘍的役割を果たします
- 細胞の競争は,新生腫瘍を排除することによって,正常な組織の整合性を維持するメカニズムとして機能します.
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