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肺転移には表皮からメゼンキマへの移行は不要ですが,化学抵抗に寄与します
Kari R Fischer1,2,3,4, Anna Durrans1,2,3, Sharrell Lee1,2,3
1Department of Cardiothoracic Surgery, Weill Cornell Medical College of Cornell University, 1300 York Avenue, New York, New York 10065, USA.
Nature
|November 13, 2015
まとめ
化学療法後の再発性乳がんの転移には,上皮細胞からメゼンキーマ細胞への移行 (EMT) が不可欠です. EMTのターゲティングは,従来の化学療法と共に治療の有効性を高める可能性があります.
科学分野:
- 腫瘍学
- 癌 生物学
- 分子生物学
背景:
- 癌の転移における上皮からメゼンキマへの移行 (EMT) の役割は,体内モニタリングの課題のために議論されている.
- EMTのダイナミクスを理解することは 効果的ながん治療法の開発に不可欠です
研究 の 目的:
- EMTを in vivoでモニタリングするための系統追跡システムを確立する.
- 乳がんの転移と化学抵抗に対するEMTの貢献を調査する.
主な方法:
- マウスにおけるメゼンキマ特有のクレム媒介の光マーカースイッチシステムの開発.
- 乳腺から肺への転移モデルを用いて
- EMTを抑制するためにマイクロRNA (miR-200) 操作を使用します.
主要な成果:
- 主要腫瘍細胞のわずかな部分はEMTを受け,転移は主に上皮性である.
- EMTの抑制は,初期肺転移の発達に影響を与えなかった.
- EMT細胞は,サイクロフォスファミドに対する生存率と化学抵抗性の増加を示し,これはmiR- 200によって逆転した.
- EMT細胞は化学療法後の転移に大きく寄与する.
結論:
- EMTは初期転移には欠かせないが,再発や化学抵抗には不可欠である.
- 化学療法と組み合わせた EMT ターゲティング戦略は 乳がんの治療に有望です
- miR-200は,EMT細胞の化学抵抗を解消する役割を果たします.
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