VEGFプロモーターの活性が腫瘍に誘発され,ストロマル細胞に作用する
D Fukumura1, R Xavier, T Sugiura
1Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital, Boston 02114, USA.
Cell
|September 30, 1998
まとめ
血管内皮成長因子 (VEGF) プロモーターの下で緑色光タンパク質 (GFP) を発現するトランス遺伝子マウスは,傷の治癒と腫瘍の成長における線維芽細胞の活性を示しています. これは,腫瘍血管新生におけるストロマ細胞の役割を強調しています.
科学分野:
- 分子生物学は分子生物学である.
- 腫瘍学 腫瘍学
- 細胞生物学 細胞生物学
背景:
- 血管内皮成長因子 (VEGF) は,新しい血管の形成である血管新生において重要な役割を果たします.
- VEGFの細胞源と調節を理解することは,がんと傷の治癒のための標的治療の開発に不可欠です.
研究 の 目的:
- VEGFプロモーターの活動をリアルタイムで視覚化するためのトランスジェニックマウスモデルを開発する.
- 傷の治癒と腫瘍発達の過程におけるVEGFプロモーター活性化の細胞の局所化とダイナミクスを調査する.
主な方法:
- VEGFプロモーターの制御下で,A. victoria緑色光タンパク質 (GFP) を発現するトランスジェニックマウスの生成.
- 表面性潰瘍性創傷の誘導とVEGF-GFPマウスに固体腫瘍の埋め込み.
- 傷や腫瘍組織におけるGFP光の顕微鏡分析.
主要な成果:
- GFPの光は,癒しの傷の縁の線維芽細胞と粒状組織の中で観察されました.
- 腫瘍の埋め込みにより,GFPの発現が増加し,宿主のVEGFプロモーターの活性化を示した.
- 光細胞,主に線維芽細胞は,腫瘍に侵入し,腫瘍全体に存在していました.
- 自発的な乳腺腫瘍は,ストロマに強いGFP発現を示したが,腫瘍細胞内にはなかった.
結論:
- 変異していないストロマル細胞,特に線維芽細胞のVEGFプロモーターは,腫瘍の微環境によって有意に活性化されます.
- フィブロブラストは,腫瘍内のVEGF駆動の血管新生において重要な役割を果たします.
- 腫瘍血管新生を理解し,標的を絞るには,ストロマ細胞の協力に関するさらなる研究が不可欠です.
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