Bv8调节了依赖于髓状细胞的瘤血管生成
Farbod Shojaei1, Xiumin Wu, Cuiling Zhong
1Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.
Nature
|December 8, 2007
概括
普罗基尼提辛-2 (Bv8) 调动骨髓中的髓状细胞,促进瘤血管生成. 用抗体阻止Bv8抑制瘤生长和血管生成,提供了一个潜在的治疗策略.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 骨髓衍生细胞对于瘤血管生成至关重要,但机制尚不清楚.
- 包括Bv8 (prokineticin 2) 在内的prokineticins调节血管新生和造血细胞动员.
- Bv8在骨髓中表达,这表明它在瘤相关的骨髓细胞调动中发挥了作用.
研究的目的:
- 阐明Bv8在瘤血管生成和髓状细胞调动中的作用.
- 为了研究骨髓状细胞中Bv8表达的调节.
- 在癌症模型中评估抗Bv8抗体的治疗潜力.
主要方法:
- 在小鼠中植入瘤以研究髓状细胞 (CD11b+Gr1+) 中Bv8表达.
- 鉴定颗粒细胞殖民地刺激因子作为Bv8.8的调节剂.
- 在体内给予抗Bv8抗体和腺病毒Bv8输送.
- 对瘤生长,血管生成和髓状细胞群的评估.
主要成果:
- 瘤细胞植入在骨髓细胞中的Bv8上调,由颗粒细胞殖民地刺激因子调节.
- 反Bv8抗体抑制了髓状细胞的动员和瘤血管生成.
- 亚地诺病毒Bv8输送促进了瘤内的血管生成.
- 抗Bv8治疗抑制了瘤生长,血管新生和髓状细胞透,对抗VEGF或化疗具有添加作用.
结论:
- Bv8在癌症中发挥着双重作用,通过调节骨髓中的髓状细胞动员和促进局部瘤血管生成.
- 向Bv8代表了抑制瘤生长和血管生成的有希望的治疗策略.
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