炎症の表皮記憶は組織損傷を制限し,臓腫瘍発生を促進する

Edoardo Del Poggetto¹, I-Lin Ho^1,2, Chiara Balestrieri^3,4

¹Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Science (New York, N.Y.)

|September 16, 2021

まとめ

臓の細胞を癌に駆り立てます炎症は治った後も持続的な変化を残し,細胞をKRAS変異に脆弱にし,管腺がん (PDAC) の発症を促進します.

科学分野:

腫瘍学
胃腸内科
細胞生物学

背景:

炎症は臓管腺がん (PDAC) の主要な危険因子です.
KRAS変異は,特にマウスモデルでの臓炎では,PDACの発症を加速する.

研究の目的:

臓上皮細胞の腫瘍性KRASに対する感受性に対する一時的な炎症の影響を調査する.
炎症解消後の臓細胞の長期的な適応反応を理解する

主な方法:

マウスモデルを用いて,炎が臓上皮細胞に及ぼす影響を研究した.
炎症的な出来事の後の転写と表遺伝子の再プログラム分析
細胞の適応と変容におけるアシナール・トゥ・ダクトル・メタプラジア (ADM) の役割を調査する.

主要な成果:

解消された炎症的イベントは,腫瘍性KRASによって変換されるために臓の上皮細胞を初期化することができます.
臓細胞は炎症後,転写および表遺伝的再プログラムを含む持続的な適応反応を示します.
この適応は,炎症に再曝露された時にADMの活性化を促進し,組織損傷を軽減します.

結論:

炎症後の持続的な細胞適応は,KRAS主導のPDACに対する感受性を高める可能性があります.
KRAS変異の活性化は,不可逆的なADMを促進し,再発性炎の状況で選択的優位性を与える可能性があります.

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