González Itziar, Luzuriaga Jon, Valdivieso Alba, Candil Manuel, Frutos Jesús, López Jaime, Hernández Luis, Rodríguez-Lorenzo Luis, Yagüe Virginia, Blanco Jose Luis, Pinto Alberto, Earl Julie
Group of Ultrasonic Resonators RESULT, Institute of Physical Technologies and Informacion, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
Signaling Lab, Department of Cell Biology and Histology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Spain.
Front Cell Dev Biol. 2023 Jan 12;10:842965. doi: 10.3389/fcell.2022.842965. eCollection 2022.
In recent years, it has been verified that collective cell migration is a fundamental step in tumor spreading and metastatic processes. In this paper, we demonstrate for the first time how low-intensity ultrasound produces long-term inhibition of collective migration of epithelial cancer cells in wound healing processes. In particular, we show how pancreatic tumor cells, PANC-1, grown as monolayers respond to these waves at frequencies close to 1 MHz and low intensities (<100 mW cm) for 48-72 h of culture after some minutes of a single ultrasound irradiation. This new strategy opens a new line of action to block the spread of malignant cells in cancer processes. Despite relevant spatial variations of the acoustic pressure amplitude induced in the assay, the cells behave as a whole, showing a collective dynamic response to acoustic performance. Experiments carried out with samples without previous starving showed remarkable effects of the LICUs from the first hours of culture, more prominent than those with experiments with monolayers subjected to fasting prior to the experiments. This new strategy to control cell migration demonstrating the effectiveness of LICUS on not starved cells opens a new line of action to study effects of ultrasonic actuation on tumor tissues with malignant cells. This is a proof-of-concept study to demonstrate the physical effects of ultrasound stimulation on tumor cell migration. An in-depth biological study of the effects of ultrasounds and underlying biological mechanisms is on-going but out of the scope of this article.
近年来,已经证实集体细胞迁移是肿瘤扩散和转移过程中的一个基本步骤。在本文中,我们首次展示了低强度超声如何在伤口愈合过程中对上皮癌细胞的集体迁移产生长期抑制作用。具体而言,我们展示了单层生长的胰腺肿瘤细胞PANC-1在单次超声照射几分钟后,如何在接近1兆赫的频率和低强度(<100毫瓦/平方厘米)下对这些波做出反应,并在培养48 - 72小时后产生响应。这种新策略为阻止癌细胞在癌症进程中的扩散开辟了一条新的作用途径。尽管在实验中诱导的声压幅度存在相关的空间变化,但细胞作为一个整体表现出对声学性能的集体动态响应。对未经预先饥饿处理的样本进行的实验表明,从培养的最初几个小时起,低强度聚焦超声就产生了显著效果,比那些在实验前对单层细胞进行饥饿处理的实验效果更显著。这种控制细胞迁移的新策略证明了低强度聚焦超声对未饥饿细胞的有效性,为研究超声驱动对含有恶性细胞的肿瘤组织的影响开辟了一条新的作用途径。这是一项概念验证研究,旨在证明超声刺激对肿瘤细胞迁移的物理效应。关于超声影响及其潜在生物学机制的深入生物学研究正在进行中,但超出了本文的范围。