Bv8は,骨髄細胞に依存する腫瘍の血管新生を調節する
Farbod Shojaei1, Xiumin Wu, Cuiling Zhong
1Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.
Nature
|December 8, 2007
まとめ
プロキネチシン-2 (Bv8) は,骨髄からの骨髄細胞を動員して腫瘍血管新生を促進します. Bv8を抗体でブロックすると,腫瘍の成長と血管新生を阻害し,潜在的な治療戦略を提供します.
科学分野:
- 腫瘍学 腫瘍学
- 免疫学 免疫学とは
- 分子生物学は分子生物学である.
背景:
- 骨髄由来細胞は腫瘍血管新生に不可欠ですが,そのメカニズムは不明です.
- プロキネチシンBv8 (プロキネチシン2) を含むプロキネチシンは,血管新生と血液細胞動員を調節する.
- Bv8は骨髄で発現し,腫瘍に関連した骨髄細胞動員における役割を示唆しています.
研究 の 目的:
- 腫瘍血管新生と骨髄細胞動員におけるBv8の役割を明らかにする.
- ミエロイド細胞におけるBv8発現の調節を調査する.
- 癌モデルにおける抗Bv8抗体の治療の可能性を評価する.
主な方法:
- 腫瘍をマウスに埋め込み,骨髄細胞 (CD11b+Gr1+) のBv8発現を研究する.
- Bv8.8の調節体として,粒細胞コロニー刺激因子の特定.
- 抗Bv8抗体の投与とアデノウイルスBv8の投与 in vivo.
- 腫瘍の成長,血管新生,および骨髄細胞集団の評価.
主要な成果:
- 腫瘍細胞の埋め込みは,骨髄細胞にBv8をアップ調節し,粒状細胞コロニー刺激因子によって調節されます.
- Anti-Bv8抗体は,骨髄細胞の動員と腫瘍血管新生を阻害した.
- アデノウイルスBv8投与は,腫瘍内の血管新生を促進しました.
- Anti-Bv8治療は,抗VEGFまたは化学療法に付加的な効果で,腫瘍の成長,血管新生,骨髄細胞の浸透を抑制しました.
結論:
- Bv8は,骨髄からの骨髄細胞の動員を調節し,局所的な腫瘍血管新生を促進することによって,癌における二重の役割を果たします.
- Bv8をターゲットにすることは,腫瘍の成長と血管新生を抑制するための有望な治療戦略です.
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