Voltage imaging reveals the dynamic electrical signatures of human breast cancer cells.
Voltage imaging reveals the dynamic electrical signatures of human breast cancer cells.
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DOI：
10.1038/s42003-022-04077-2
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发表时间：
2022-11-11
影响因子：
5.9
通讯作者：
Foust, Amanda J.
中科院分区：
文献类型：
--
作者：
Quicke, Peter;Sun, Yilin;Arias-Garcia, Mar;Beykou, Melina;Acker, Corey D.;Djamgoz, Mustafa B. A.;Bakal, Chris;Foust, Amanda J.
癌细胞具有与正常细胞相比去极化的静息膜电位（Vm），并表达活性离子电导，这直接影响其病理生理学行为。尽管与“可兴奋”组织相似，但对癌细胞Vm动力学知之甚少。在这里，高通量，细胞分辨率Vm成像揭示，Vm波动动态在几个乳腺癌细胞系相比，非癌MCF-10A细胞。我们表征了数百个人三阴性乳腺癌MDA-MB-231细胞的Vm波动。通过无监督的机器学习协议量化他们的动态电子签名（DES），我们确定了四个类别，从“嘈杂”到“闪烁/挥手”。电压门控钠通道阻断剂河豚毒素、钙激活钾通道抑制剂蜂毒肽和伊比利亚毒素可抑制MDA-MB-231细胞Vm的自发性、短暂性超极化。MCF-10A细胞的Vm相对稳定，但在用转化生长因子-β1（上皮向间充质转化的典型诱导剂）处理后波动增加。这些数据表明，产生Vm波动的能力可能是杂交上皮-间充质细胞或源自管腔祖细胞的细胞的特性。电压成像和机器学习揭示了人类乳腺癌细胞表现出非致瘤性乳腺细胞中不存在的电压波动，开始揭示癌症过程的生物电特性。
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 cell Vm dynamics. Here high-throughput, cellular-resolution Vm imaging reveals that Vm fluctuates dynamically in several breast cancer cell lines compared to non-cancerous MCF-10A cells. We characterize Vm fluctuations of hundreds of human triple-negative breast cancer MDA-MB-231 cells. By quantifying their Dynamic Electrical Signatures (DESs) through an unsupervised machine-learning protocol, we identify four classes ranging from "noisy” to “blinking/waving“. The Vm of MDA-MB-231 cells exhibits spontaneous, transient hyperpolarizations inhibited by the voltage-gated sodium channel blocker tetrodotoxin, and by calcium-activated potassium channel inhibitors apamin and iberiotoxin. The Vm of MCF-10A cells is comparatively static, but fluctuations increase following treatment with transforming growth factor-β1, a canonical inducer of the epithelial-to-mesenchymal transition. These data suggest that the ability to generate Vm fluctuations may be a property of hybrid epithelial-mesenchymal cells or those originated from luminal progenitors. Voltage imaging and machine learning reveal that human breast cancer cells exhibit voltage fluctuations absent in non-tumorigenic breast cells, beginning to shed light on the bioelectric properties of cancer processes.
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影响因子：
64.8
作者：
Harris CR;Millman KJ;van der Walt SJ;Gommers R;Virtanen P;Cournapeau D;Wieser E;Taylor J;Berg S;Smith NJ;Kern R;Picus M;Hoyer S;van Kerkwijk MH;Brett M;Haldane A;Del Río JF;Wiebe M;Peterson P;Gérard-Marchant P;Sheppard K;Reddy T;Weckesser W;Abbasi H;Gohlke C;Oliphant TE
通讯作者：
Oliphant TE
影响因子：
6.4
作者：
Hernandez-Plata, Everardo;Ortiz, Cindy S.;Gomora, Juan C.
通讯作者：
Gomora, Juan C.
影响因子：
4
作者：
Campbell, Thomas M.;Main, Martin J.;Fitzgerald, Elizabeth M.
通讯作者：
Fitzgerald, Elizabeth M.
影响因子：
5.6
作者：
Guzel, R. Mine;Ogmen, Kazim;Djamgoz, Mustafa B. A.
通讯作者：
Djamgoz, Mustafa B. A.
在可塑性和杂化E/M状态下，上皮到间质转变。
影响因子：
3.9
作者：
Bornes L;Belthier G;van Rheenen J
通讯作者：
van Rheenen J