在骨髓细胞中删除血管内皮生长因子加速了瘤的产生
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
概括
从瘤中的髓状细胞中删除VEGF-A会阻断血管形成,导致瘤生长速度减慢,化疗效率提高. 这一意想不到的发现揭示了骨髓系衍生的VEGF-A.
科学领域:
- 在瘤学瘤学.
- 血管生物学 血管生物学
- 免疫学 免疫学 免疫学
背景情况:
- 瘤的进展依赖于血管生成,由诸如VEGF-A.这样的因素驱动.
- 髓状细胞,特别是巨细胞,透到瘤中,并且经常表达VEGF-A.
研究的目的:
- 研究炎症细胞衍生的VEGF-A在瘤血管化和进展中的作用.
- 确定骨髓特异性VEGF-A删除对瘤生长和治疗反应的影响.
主要方法:
- 在小鼠瘤模型中的髓状细胞中遗传删除VEGF-A.
- 对瘤血管结构,周细胞覆盖率和VEGFR2酸化的分析.
- 评估瘤生长,细胞死亡,缺氧和化学敏感性.
主要成果:
- 骨髓体VEGF-A减弱高密度血管网络形成的删除,表明血管正常化.
- 骨髓体VEGF-A的损失降低了VEGFR2酸化,但加速了瘤的进展,减少了细胞死亡,减少了缺氧.
- 缺乏髓质VEGF-A的瘤对化疗剂的敏感性增加.
结论:
- 来自骨髓细胞的VEGF-A对瘤血管化和VEGFR2信号传递至关重要,矛盾的是,它减缓了瘤的进展.
- 向骨髓体VEGF-A可能是增强抗癌疗法的新策略.
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