ネクロプトーシス微生物環境は,肝がんにおける血統結合を指示する
Marco Seehawer1,2, Florian Heinzmann1,2, Luana D'Artista1,2
1Department of Internal Medicine VIII, University Hospital Tuebingen, Tuebingen, Germany.
Nature
|September 14, 2018
まとめ
肝臓の微小環境は肝臓がんの種類に影響します アポプトティック細胞は肝臓細胞がん (HCC) を促進し,死細胞は肝臓内胆管がん (ICC) を促進する.
科学分野:
- 腫瘍学
- 分子生物学
- エピジェネティクス
背景:
- 肝臓細胞がん (HCC) と肝臓内胆管がん (ICC) を含む原発性肝臓がんは,健康に重大な負担を及ぼします.
- HCCとICCの特徴は異なる発達経路を示唆しますが,規制メカニズムは不明です.
研究 の 目的:
- 肝臓の微小環境が肝臓の腫瘍形成にどのように影響するかを調査する.
- 変異した肝細胞のHCCまたはICCへの分化を促す分子因子と表遺伝的メカニズムを特定する.
主な方法:
- 腫瘍性変異した肝細胞による肝臓腫瘍形成のモザイクマウスモデルを使用した.
- 肝臓の微小環境を分析し,細胞死経路 (アポプトーシス vs ネクロプトーシス) に焦点を当てました.
- 生成したHCCおよびICC組織のエピジェノームとトランスクリプトームのプロファイリングを行った.
主要な成果:
- 肝臓の微生物環境は,変異した肝細胞の血統結合を表遺伝的に決定する.
- ネクロプトーシスに関連したサイトカイン環境はICCを促進し,アポプトティック環境はHCCを促進する.
- Tbx3とPrdm5をヒトに保存された,遺伝学的に調節された,微環境に依存する重要な因子として特定した.
結論:
- 肝臓の微小環境は,発生する特定の肝臓がんの種類を決定する上で重要な役割を果たします.
- 微環境によるTbx3やPrdm5のような因子の表遺伝的調節は,様々な肝臓に害を与える因子がHCCやICCに繋がる理由を説明します.
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