Cell swelling, softening and invasion in a three-dimensional breast cancer model
Cell swelling, softening and invasion in a three-dimensional breast cancer model
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DOI：
10.1038/s41567-019-0680-8
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发表时间：
2020-01-01
期刊：
影响因子：
19.6
通讯作者：
Guo, Ming
中科院分区：
文献类型：
--
作者：
Han, Yu Long;Pegoraro, Adrian F.;Guo, Ming
三维多细胞组织的结构和功能的控制关键取决于细胞物理特性的空间和时间协调，但管理这些事件及其在疾病中的破坏的组织原则仍然知之甚少。使用多细胞乳腺癌类器官模型，我们在这里映射的位置，运动和三维的单个细胞的物理特性的时空演变。与类器官核心中的细胞相比，类器官外围和侵入前沿的细胞被发现系统地更柔软，更大，更有活力。这些机械变化是由细胞外液流经缝隙连接引起的，对缝隙连接的抑制会延迟向侵袭性表型的转变。这些发现强调了组织和疾病进展中细胞物理特性的时空协调的作用。
Control of the structure and function of three-dimensional multicellular tissues depends critically on the spatial and temporal coordination of cellular physical properties, yet the organizational principles that govern these events and their disruption in disease remain poorly understood. Using a multicellular mammary cancer organoid model, we map here the spatial and temporal evolution of positions, motions and physical characteristics of individual cells in three dimensions. Compared with cells in the organoid core, cells at the organoid periphery and the invasive front are found to be systematically softer, larger and more dynamic. These mechanical changes are shown to arise from supracellular fluid flow through gap junctions, the suppression of which delays the transition to an invasive phenotype. These findings highlight the role of spatiotemporal coordination of cellular physical properties in tissue organization and disease progression.