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血液流动将细胞外囊泡从内皮退化部分转移,以促进血管生成
Benjamin Mary1,2,3,4, Nandini Asokan1,2,3,4, Katerina Jerabkova-Roda1,2,3,4
1INSERM UMR_S1109, Strasbourg, France.
EMBO reports
|November 16, 2023
概括
瘤细胞外囊泡 (tEVs) 在血液流量较低时被内皮细胞吸收,将它们从降解中重新引导. 这一过程增强了它们的前瘤功能,有助于转移前的位形成.
科学领域:
- 在瘤学瘤学.
- 血管生物学 血管生物学
- 细胞机械生物学 细胞机械生物学
背景情况:
- 瘤细胞外囊泡 (tEVs) 循环并改变遥远的器官微环境,促进转移.
- 血液流动动力学 (血液动力学) 对循环tEV功能的影响尚不清楚.
研究的目的:
- 研究血动力学如何影响内皮细胞对瘤细胞外囊泡 (tEVs) 的吸收和细胞内贩运.
- 阐明血动力学介导的tEV处理对内皮细胞和血管生成的功能后果.
主要方法:
- 用于体外内皮细胞培养,经过不同流量条件.
- 采用了追踪tEV吸收和细胞内贩运的技术,包括Rab14阳性内体和溶酶体.
- 评估了亲血管生成因子的表达,并在斑马鱼中进行了体内血管生成试验.
主要成果:
- 在低流量模式中的内皮细胞表现出对tEVs的增强吸收.
- 低流量条件将内部化的tEVs重定向到Rab14阳性内体,绕过 lysosomal 降解.
- 在低流量刺激的内皮细胞中的tEVs促进亲血管性转录因子表达和血管发芽.
结论:
- 血液动力学,特别是静脉的低流量,增强了循环tEVs的前瘤功能.
- 内皮细胞机械感应使tEVs从降解中转移,促进它们的亲血管性信号传递.
- tEV利用血液动力学来促进特定血管区域的前转移性利基形成.
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