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肝臓の星状細胞のサブ集団が肝臓がん発生における対極的な役割
Aveline Filliol1, Yoshinobu Saito1, Ajay Nair1,2
1Department of Medicine, Columbia University, New York, NY, USA.
Nature
|October 5, 2022
まとめ
肝臓の星状細胞 (HSC) は肝臓がんにおいて二重の役割を果たします. 当初は保護的であったが,腫瘍促進状態への移行は,慢性肝疾患における肝細胞癌 (HCC) の発症を誘発する.
科学分野:
- ヘパトロジー
- 癌 生物学
- 繊維症の研究
背景:
- 肝細胞癌 (HCC) は,がんによる主要な死亡原因であり,主に慢性肝疾患および進行性線維症の患者で発生する.
- 肝臓の星状細胞 (HSC) は肝臓の主要な線維芽細胞であり,肝臓の病理生物学において重要な役割を果たします.
研究 の 目的:
- 肝臓の星状細胞 (HSC) の多面的な機能を肝臓がん発生過程で調査する.
- HSC亜集団が肝細胞の行動と腫瘍の発達に影響を与えるメカニズムを解明する.
主な方法:
- HSCの遺伝子操作 (枯渇,活性化,抑制) によるHCCのマウスモデルを使用した.
- マウスとヒトのHSC亜集団を分析するために単細胞RNA配列を解析した.
- 遺伝子剥離によるサブ集団特有のメディエーターの役割を調査した.
主要な成果:
- HSCは,肝細胞増殖と死亡を調節するプレネプラスティック環境で濃縮されていることが判明しました.
- 静止状態でサイトカインを産生するHSCは,肝細胞成長因子を産生し,HCCに対する保護を与えました.
- マトリックス硬化とTAZ活性化によって腫瘍の発達を促進する.
結論:
- HSCは,保護作用から腫瘍促進作用へのダイナミックなシフトとともに,肝がん発生において二重の機能を発揮する.
- 慢性肝疾患の進行中のHSCサブ集団の不均衡は,HCCのリスクの増加と相関しています.
- HSCサブポピュレーションとそのメディエーターをターゲットにすることで,HCCの予防と治療のための治療戦略を提供することができます.
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