Membrane voltage fluctuations in human breast cancer cells
Membrane voltage fluctuations in human breast cancer cells
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人类乳腺癌细胞的膜电压波动
DOI：
10.1101/2021.12.20.473148
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Quicke P
中科院分区：
文献类型：
--
作者：
Quicke P
癌细胞具有静息膜电位(Vm)，与正常细胞相比去极化，并表达活性离子电导，这直接影响其病理生理行为。尽管与“可兴奋”的组织有相似之处，但人们对癌细胞的血管动力学知之甚少。利用高通量、细胞分辨率的Vm成像，我们表征了数百个三阴性乳腺癌MDA-MB-231细胞的Vm波动，并与非癌乳腺上皮MCF-10A细胞进行了比较。通过一种无监督的机器学习协议对他们的动态电信号(DESS)进行量化，我们识别了四种类别，从“嘈杂的”到“眨眼/挥手”。电压门控性钠通道阻滞剂河豚毒素可抑制MDA-MB-231细胞的Vm，表现出自发的、短暂的超极化。MCF10A细胞的Vm值相对稳定，但经转化生长因子-β1处理后波动增加，转化生长因子是上皮向间充质转化的典型诱导剂。这些数据表明，产生Vm波动的能力是在转化过程中获得的，可能参与了肿瘤的发生。
Cancer cells feature a resting membrane potential (Vm) that is depolarized compared to normal cells, and express active ionic conductances, which factor directly in their pathophysiological behavior. Despite similarities to ‘excitable’ tissues, relatively little is known about cancer cellVmdynamics. With high-throughput, cellular-resolutionVmimaging, we characterizedVmfluctuations of hundreds of human triple-negative breast cancer MDA-MB-231 cells and compared to non-cancerous breast epithelial MCF-10A cells. By quantifying their Dynamic Electrical Signatures (DESs) through an unsupervised machine-learning protocol, we identified four classes ranging from “noisy” to “blinking/waving”. TheVmof MDA-MB-231 cells exhibited spontaneous, transient hyperpolarizations that were inhibited by the voltage-gated sodium channel blocker tetrodotoxin. TheVmof MCF-10A cells was comparatively static, but fluctuations increased following treatment with transforming growth factor-β1, a canonical inducer of the epithelial-to-mesenchymal transition. These data suggest that the ability to generateVmfluctuations is acquired during transformation and may participate in oncogenesis.
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DOI：
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发表时间：
2001-12
期刊：
--
影响因子：
--
作者：
A. Destexhe;T. Sejnowski
通讯作者：
A. Destexhe;T. Sejnowski
影响因子：
7.2
作者：
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影响因子：
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作者：
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影响因子：
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作者：
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