Topological defects in the mesothelium suppress ovarian cancer cell clearance.
Topological defects in the mesothelium suppress ovarian cancer cell clearance.
复制标题
间皮层的拓扑缺陷抑制卵巢癌细胞的清除。
DOI：
10.1063/5.0047523
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发表时间：
2021-09
影响因子：
6
通讯作者：
Notbohm J
中科院分区：
文献类型：
--
作者：
Zhang J;Yang N;Kreeger PK;Notbohm J
我们研究了一种间皮细胞清除的体外模型，其中卵巢癌细胞侵入间皮细胞层，导致间皮细胞回缩与癌细胞解聚和扩散相结合。在加入肿瘤细胞之前，间皮细胞具有细长的形态，使它们与相邻的细胞排列成有序的结构域。这种排列中的缺陷发生在拓扑缺陷处，与细胞密度、运动和力的改变有关。在这里，我们确定了拓扑缺陷的间皮层，并显示了它们如何影响局部细胞密度，产生一个净流量的细胞向内或向外，这取决于缺陷类型。在净流入的位置，间皮清除受阻。因此，由拓扑缺陷支配的间皮细胞的集体行为影响肿瘤细胞的清除和扩散。重要的是，我们的发现在多种卵巢癌细胞类型中是一致的，这表明了一种可能影响卵巢癌转移的新的物理机制。
We investigated an in vitro model for mesothelial clearance, wherein ovarian cancer cells invade into a layer of mesothelial cells, resulting in mesothelial retraction combined with cancer cell disaggregation and spreading. Prior to the addition of tumor cells, the mesothelial cells had an elongated morphology, causing them to align with their neighbors into well-ordered domains. Flaws in this alignment, which occur at topological defects, have been associated with altered cell density, motion, and forces. Here, we identified topological defects in the mesothelial layer and showed how they affected local cell density by producing a net flow of cells inward or outward, depending on the defect type. At locations of net inward flow, mesothelial clearance was impeded. Hence, the collective behavior of the mesothelial cells, as governed by the topological defects, affected tumor cell clearance and spreading. Importantly, our findings were consistent across multiple ovarian cancer cell types, suggesting a new physical mechanism that could impact ovarian cancer metastasis.
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影响因子：
16.6
作者：
Domcke, Silvia;Sinha, Rileen;Levine, Douglas A.;Sander, Chris;Schultz, Nikolaus
通讯作者：
Schultz, Nikolaus
影响因子：
6
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
64.8
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Carreiras, Franck