ミエロイド細胞における血管内皮成長因子の除去は,腫瘍発生を加速する

Christian Stockmann¹, Andrew Doedens, Alexander Weidemann

¹Molecular Biology Section, Division of Biological Sciences, Moores Cancer Center, University of California, San Diego, San Diego, California 92093, USA.

Nature

|November 11, 2008

まとめ

腫瘍の骨髄細胞からVEGF-Aを削除すると,血管形成が阻害され,腫瘍の成長が遅くなり,化学療法の効果が向上します. この予期せぬ発見は,骨髄系由来のVEGF-Aを明らかにしています.

科学分野:

腫瘍学腫瘍学
血管生物学血管生物学
免疫学免疫学とは

背景:

腫瘍の進行は血管新生に依存し,VEGF-A.のような要因によって引き起こされます.
ミエロイド細胞,特にマクロファージは腫瘍に浸透し,しばしばVEGF-Aを発現する.

研究の目的:

腫瘍の血管化と進行における炎症細胞由来VEGF-Aの役割を調査する.
腫瘍の成長と治療への反応に対する,骨髄組織特異のVEGF-Aの欠失の影響を決定する.

主な方法:

ネズミの腫瘍モデルにおける骨髄細胞におけるVEGF-Aの遺伝的消去.
腫瘍の血管構造,ペリサイトの覆い,VEGFR2のリン酸化の分析.
腫瘍の成長,細胞死,低酸素,化学反応に対する感受性の評価.

主要な成果:

ミエロイドのVEGF-Aの消去が衰弱した高密度血管ネットワーク形成であり,血管の正常化を示している.
ミエロイドVEGF-Aの喪失はVEGFR2のリン酸化を低下させましたが,腫瘍の進行を加速し,細胞死亡を減少させ,低酸素症を減少させました.
ミエロイドVEGF-Aが欠けていた腫瘍は,化学療法剤に対する感受性の増加を示した.

結論:

ミエロイド由来のVEGF-Aは,腫瘍の血管化とVEGFR2のシグナル伝達に不可欠であり,逆説的に腫瘍の進行を遅らせます.
ミエロイドVEGF-Aをターゲットにすることは,抗がん療法を強化するための新しい戦略を代表する可能性があります.

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