Invasiveness research is an essential step in breast cancer metastasis. The application of high-frequency ultrasound microbeam stimulation (HFUMS) offers a manner of determining the invasion potential of human breast cancer cells by eliciting the elevation of transient cytoplasmic calcium ions (Ca2+). The fluorescent index (FI), which is a composite parameter reflecting calcium elevations elicited by HFUMS, was shown to be higher in invasive breast cancer cells (MDA-MB-231) compared to weakly invasive breast cancer cells (MCF-7) using the low-intensity 50-MHz HFUMS. This novel finding shows significant difference from the reported studies in which MCF-7 cells showed no response to HFUMS. In addition to the negligible response of normal human breast cells (MCF-10A), HFUMS shows the potential to be capable of differentiating the normal cells from the cancer cells. To understand the mechanism of HFUMS worked on mechanotransduction in cells, different channel blockers were used to investigate the roles of specific channels during HFUMS. It was found that GsMTx4 (30 μM), a selective blocker of mechanosensitive Piezo channels, reduces the FI values significantly in MDA-MB-231 cells, while SKF-96365 (40 μM), a general TRP channel blocker, cannot induce the significant inhibition of FI values. The results indicate that Piezo channels may play the main role in invasion and metastatic propagation of cells.

中文翻译：

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非接触式高频超声微束刺激：细胞反应的新发现和潜在原因

侵袭性研究是乳腺癌转移的重要步骤。高频超声微束刺激 (HFUMS) 的应用提供了一种通过引起瞬时细胞质钙离子 (Ca2+) 升高来确定人类乳腺癌细胞侵袭潜力的方法。与弱浸润性乳腺癌细胞 (MCF-7) 相比，荧光指数 (FI) 是反映 HFUMS 引起的钙升高的复合参数，在浸润性乳腺癌细胞 (MDA-MB-231) 中显示更高。低强度 50-MHz HFUMS。这一新发现与报道的 MCF-7 细胞对 HFUMS 没有反应的研究有显着差异。除了正常人乳腺细胞（MCF-10A）的反应可以忽略不计，HFUMS 显示出能够将正常细胞与癌细胞区分开来的潜力。为了了解 HFUMS 在细胞机械转导中的作用机制，使用不同的通道阻滞剂来研究特定通道在 HFUMS 过程中的作用。发现机械敏感压电通道的选择性阻断剂 GsMTx4 (30 μM) 显着降低 MDA-MB-231 细胞中的 FI 值，而通用 TRP 通道阻断剂 SKF-96365 (40 μM) 不能诱导显着的FI 值的抑制。结果表明压电通道可能在细胞的侵袭和转移增殖中起主要作用。发现机械敏感压电通道的选择性阻断剂 GsMTx4 (30 μM) 显着降低 MDA-MB-231 细胞中的 FI 值，而通用 TRP 通道阻断剂 SKF-96365 (40 μM) 不能诱导显着的FI 值的抑制。结果表明压电通道可能在细胞的侵袭和转移增殖中起主要作用。发现机械敏感压电通道的选择性阻断剂 GsMTx4 (30 μM) 显着降低 MDA-MB-231 细胞中的 FI 值，而通用 TRP 通道阻断剂 SKF-96365 (40 μM) 不能诱导显着的FI 值的抑制。结果表明压电通道可能在细胞的侵袭和转移增殖中起主要作用。