CD93维持了内皮屏障功能,并限制了转移性传播
Kalyani Vemuri1, Beatriz de Alves Pereira1, Patricia Fuenzalida1
1Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Science for Life Laboratory, and.
JCI insight
|March 5, 2024
概括
CD93蛋白对于保持血管完整性和预防癌症扩散至关重要. 在黑色素瘤模型中,其缺席增加了转移,突出显示CD93是抗血管原治疗的潜在治疗点.
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:
- 损害血管完整性是癌细胞扩散和转移传播的关键驱动因素.
- CD93是抗血管生成疗法的已知标,但它在维持转移性癌症中的血管完整性方面的作用尚不清楚.
研究的目的:
- 研究CD93在维持内皮屏障功能的作用及其对癌症转移传播的影响.
主要方法:
- 利用CD93淘汰赛 (CD93-/-) 小鼠和野生类型的 littermates 来研究原发性黑色素瘤的生长和转移.
- 通过检查附着物和紧密的结合点来评估内皮膜屏障的完整性.
- 在转移部位测量了矩阵金属蛋白酶9 (MMP-9) 表达.
- 研究了CD93和血管内皮生长因子受体2 (VEGFR2) 之间的相互作用.
- 进行抗VEGFR2抗体治疗,以评估其对血管完整性和转移的影响.
主要成果:
- 尽管主要瘤生长受阻,但CD93-/-小鼠表现出转移扩散的增加.
- 缺少CD93导致瘤内皮细胞的附着和紧密结合被破坏,并增加了MMP-9的表达.
- CD93与VEGFR2直接相互作用;它的缺失导致了VEGF诱导的VEGFR2.2的高酸化.
- 抗VEGFR2抗体治疗恢复了内皮屏障功能,并减少了CD93-/-小鼠的转移负担.
结论:
- CD93在维持内皮屏障完整性和抑制转移传播方面发挥着至关重要的作用.
- 向CD93或其与VEGFR2的相互作用可能为控制癌症病理血管生成和转移提供治疗策略.
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