エピテリア腫瘍発生に反応してp53の損失を伴うストロマルメゼンキームの選択的進化
Reginald Hill1, Yurong Song, Robert D Cardiff
1Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Cell
|December 20, 2005
まとめ
癌の進行には,単に腫瘍細胞だけではありません. エピテリアストレスは,腫瘍の微小環境における線維細胞変異,特にp53喪失を非自律的に選択することがあります.
科学分野:
- 腫瘍学 腫瘍学
- がん生物学 がん生物学
- 腫瘍マイクロ環境の研究
背景:
- 癌の理解は,伝統的に腫瘍細胞の異常に焦点を当てています.
- フィブロブラストを含む腫瘍のマイクロ環境は,腫瘍発生に大きく影響する.
- 証拠は,腫瘍の進行中にストロマ細胞における遺伝的/表遺伝的変化の非自律的な選択を示唆しています.
研究 の 目的:
- 線維芽細胞が,上皮からの腫瘍性ストレスによる遺伝的/表遺伝的変化を被っているかどうかを実験的に評価する.
- 癌発達の過程でストロマ細胞の異常を誘導する細胞間通信の役割を調査する.
主な方法:
- 前立腺がんのマウスモデルを利用した.
- pRb機能を阻害することによって誘発された上皮細胞サイクル障害.
- 関連する線維芽細胞におけるパラクリン信号応答を分析した.
- 選択的圧力下での繊維細胞増殖とp53の状態の評価.
主要な成果:
- 皮質細胞循環の障害は,線維芽細胞におけるパラクリンp53応答を誘発した.
- このパラクリン信号伝達は,正常な線維芽細胞の増殖を抑制した.
- ストロマに強い選択的圧力が加えられた.
- その結果生じたメゼンキムは,高い増殖と取得したp53損失を示した.
結論:
- 腫瘍の微小環境内の細胞間通信は,構造変異の非自律的な選択を促します.
- エピテリウムにおける腫瘍性ストレスは,線維芽細胞における腫瘍抑制遺伝子喪失 (p53) の選択につながる可能性があります.
- このメカニズムは,線維芽細胞のコンパートメントを変化させることで,腫瘍の進行に貢献します.
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