老化に関連した再プログラミングは,がんの根性を促進します
Maja Milanovic1, Dorothy N Y Fan1,2,3,4, Dimitri Belenki1
1Charité - Universitätsmedizin Berlin, Medical Department of Hematology, Oncology and Tumor Immunology, and Molekulares Krebsforschungszentrum - MKFZ, Virchow Campus, 13353 Berlin, Germany.
Nature
|December 21, 2017
まとめ
化学療法によって引き起こされる細胞老化は 予期せぬ形で 癌の幹を強化し より攻撃的な腫瘍や 再発につながる可能性があります 癌細胞の成長と 腫瘍の発生の可能性を高めます
科学分野:
- 腫瘍学
- 細胞生物学
- 癌 の 幹 細胞 生物学
背景:
- 細胞の衰えは 細胞の循環を 保護するものです 幹細胞の機能 (幹性) も制御する.
- 癌細胞の幹細胞が増加すると 腫瘍が攻撃的になり 臨床結果が悪くなります
研究 の 目的:
- 化学療法による老化が悪性細胞の幹細胞関連特性を変化させるかどうかを調査する.
- 癌の攻撃性や治療結果に対する 衰老に関連した茎の影響を理解する.
主な方法:
- 遺伝子発現とEμ-Myc変異マウスの老化および非老化B細胞リンパ腫の機能分析
- H3K9me3またはp53を標的とした遺伝的に切り替え可能なモデルを使用して,老化脱出を研究した.
- 急性リンパ性および骨髄性白血病のp53調節可能なモデルでの老化強化を調査した.
主要な成果:
- 衰老性リンパ腫は 成人幹細胞のシグネチャーを増幅し Wntシグネチャーを活性化し 異なる幹細胞マーカーを示しました
- 衰老を逃れた細胞は,Wnt依存のクローノジェニック成長と,in vivoではより高い腫瘍発症の可能性を示した.
- 暫定的な衰老誘導により 幹細胞以外の白血病細胞は 自己再生性で白血病を誘発する 幹細胞に再プログラムされました
結論:
- 衰老に関連した幹は,細胞サイクル停止から解放されたときに癌細胞の攻撃性を高める固有の特徴です.
- この現象は,特に再発の場合には,がん治療に重大な影響を及ぼします.
- 発見は癌細胞の可塑性を明らかにし 腫瘍の再発に関する新しい仕組みの洞察を提供します
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