在侵袭前线的矩阵机械感应会诱导细胞骨和转录记忆,支持转移
Oscar Maiques1,2,3,4, Marta C Sallan1,5, Roman Laddach6,7
1Cytoskeleton and metastasis Team, The Breast Cancer Now Toby Robins Research Centre Division of Breast Cancer Research, The Institute of Cancer Research, Chester Beatty Laboratories, London, SW3 6JB, UK.
Nature communications
|February 14, 2025
概括
细胞外矩阵 (ECM) 组织决定了瘤的扩散. 侵入性瘤表现出改变的ECM,转移反映了这些特征,揭示了影响癌症进展和预后的空间记忆.
科学领域:
- 在瘤学瘤学.
- 生物物理学的生物物理.
- 癌症生物学 癌症生物学
背景情况:
- 细胞外基质 (ECM) 在调节瘤细胞行为,包括侵袭和转移方面发挥着至关重要的作用.
- 了解ECM在不同瘤区域内的特定组织对于破译它对癌症传播的影响至关重要.
研究的目的:
- 描述ECM在人类和小鼠瘤中的三维组织.
- 调查ECM特征和侵入性表型之间的相关性.
- 为了确定转移性瘤是否重复其主要部位的ECM特征.
主要方法:
- 在人类和小鼠瘤样本中ECM组织的表征,区分瘤体,近端侵袭前端和远端侵袭前端.
- 在实验室培养来自不同瘤区域的小鼠癌细胞,以评估空间细胞骨和转录记忆.
- 开发体外模型来模仿体内ECM组织,并研究其对癌细胞入侵的影响.
- 空间转录学用于识别与ECM组织和患者预后相关的分子程序.
主要成果:
- 与瘤体相比,侵入性瘤区域表现出增加的矩阵密度,纤维厚度,长度和对齐.
- 距离侵袭前部独特的辐射纤维定向与阿米类侵袭特征相关.
- 发现转移复制了原发性瘤的ECM特征.
- 实验室模型证实,增加矩阵密度促进3D封闭和Rho-ROCK-Myosin II活性,而辐射方向增强了定向入侵.
- 空间转录学揭示了一种机械炎症程序,与各种癌症类型的更差预后有关.
结论:
- ECM组织是瘤入侵和转移的关键决定因素.
- 瘤细胞对其ECM环境具有空间记忆,影响其侵入性行为.
- ECM机制和细胞反应之间的相互作用,包括机械炎症程序,有助于癌症的进展,并预测患者的结果.
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