多细胞力协调构建微通道网络,在细胞外基质中进行无障碍的转移
Huan Gao1,2,3,4, Bo Cheng2,4,5, Guorui Jin2,4
1Phase I Clinical Trial Research Center, The First Affiliated Hospital of Xi'an Jiaotong University, Shaanxi 710061, P.R. China.
Science advances
|December 19, 2025
概括
癌细胞在细胞外基质中协同构建相互连接的微通道网络,创建促进转移的"超级高速公路". 这种协调的行动涉及机械桥梁和领导细胞,揭示了一个自我组织的转移性系统.
科学领域:
- 癌症生物学 癌症生物学
- 细胞力学 细胞力学
- 生物物理学的生物物理.
背景情况:
- 细胞外基质 (ECM) 是癌症转移的物理障碍.
- 之前的研究集中在单个癌细胞ECM重塑上.
- 多细胞通信在ECM转移转移重编程中的作用尚不清楚.
研究的目的:
- 研究癌细胞如何协同重塑ECM.
- 揭示转移性微通道网络形成背后的机制.
- 为了识别参与这个过程的细胞组件和信号通路.
主要方法:
- 活细胞成像用于观察动态过程.
- 原子力显微镜和光学子探测机械性能.
- 单细胞测序用于分析细胞状态.
- 基于网格之外的代理模型来模拟网络形成.
主要成果:
- 癌细胞协同重编程ECM,形成相互连接的微通道网络.
- 由基于原的机械桥梁引导的相邻通道的有组织的交叉融合是至关重要的.
- 机械响应的领导细胞,表达特定的信号分子 (integrin-RhoA/YAP) 和酶 (矩阵金属蛋白酶14),启动网络建设.
- 这些网络的作用是:
结论:
- 癌细胞通过协调ECM重编程创建自我组织的转移性网络.
- 通过原桥传递的机械线索直接指导多细胞力协调.
- 领导者细胞在启动这些转移性超级高速公路的形成中发挥着关键作用.
- 这项研究为了解转移和潜在的治疗点提供了新的框架.
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