Yoda1 Enhanced Low-Magnitude High-Frequency Vibration on Osteocytes in Regulation of MDA-MB-231 Breast Cancer Cell Migration.
Yoda1 Enhanced Low-Magnitude High-Frequency Vibration on Osteocytes in Regulation of MDA-MB-231 Breast Cancer Cell Migration.
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DOI：
10.3390/cancers14143395
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发表时间：
2022-07-13
期刊：
影响因子：
5.2
通讯作者：
You, Lidan
中科院分区：
文献类型：
--
作者：
Lin, Chun-Yu;Song, Xin;Ke, Yaji;Raha, Arjun;Wu, Yuning;Wasi, Murtaza;Wang, Liyun;Geng, Fei;You, Lidan
关键词：
骨转移是乳腺癌的一种严重并发症，是乳腺癌患者发病率和死亡率的重要原因。虽然机械负荷被证明可以介导骨重建和减弱转移性肿瘤的生长，但通常规定的运动对癌症患者来说可能是身体上的挑战。低幅高频（LMHF）振动作为一种运动替代方案，可提高骨密度，同时安全且易于执行。然而，单独的振动似乎不足以减少乳腺癌引起的骨质流失。Yoda 1是机械敏感Piezo 1通道的激活剂，提供了一种潜在的解决方案来强化LMHF振动的影响。本研究旨在探讨联合治疗（Yoda 1和LMHF振动）在调节破骨细胞生成和乳腺癌细胞迁移中的作用。我们证实，结合LMHF振动和Yoda 1减少破骨细胞的形成，并进一步抑制MDA-MB-231乳腺癌细胞的迁移。我们的数据支持调节高危患者癌细胞迁移的新策略。低幅值（≤1 g）高频（≥30 Hz）（LMHF）振动已被证明可提高骨密度。然而，其在乳腺癌骨转移中的调节对于乳腺癌患者和老年人群仍然存在争议。Yoda 1是机械敏感性Piezo 1通道的激活剂，可以通过增强骨细胞的机械响应来潜在地增强LMHF振动的效果，骨细胞是具有高表达Piezo 1的主要机械感觉骨细胞。在这项研究中，我们处理骨细胞与单（Yoda 1或振动）或联合治疗（Yoda 1和LMHF振动），并检查破骨细胞和乳腺癌细胞通过条件培养基的进一步调节。此外，我们还研究了联合治疗对乳腺癌细胞骨细胞调节的影响。联合处理对骨细胞显示出有益的作用，包括增加骨细胞中的Yes相关蛋白（雅普）的核转位（488.0%，p < 0.0001），抑制破骨细胞生成（34.3%，p = 0.004），并且进一步降低MDA-MB-231（15.1%，p = 0.02）而不是Py 8119乳腺癌细胞（4.2%，p = 0.66）的迁移。最后，MDA-MB-231乳腺癌细胞进行的联合治疗的凋亡骨细胞的百分比降低（34.5%，p = 0.04），但不影响细胞内钙流入。这项研究显示了刺激Piezo 1在增强骨细胞对LMHF振动的机械反应和进一步抑制乳腺癌通过破骨细胞迁移方面的潜力。
Bone metastasis is a severe complication that contributes significantly to the morbidity and mortality of breast cancer patients. Although mechanical loading was shown to mediate bone remodeling and attenuate metastatic tumor growth, commonly prescribed exercise can be physically challenging for cancer patients. Low-magnitude high-frequency (LMHF) vibration as an exercise alternative enhances bone mineral density while being safe and easy-to-perform. However, vibration alone appears to be insufficient in reducing bone loss caused by breast cancer. Yoda1, an activator of the mechanosensitive Piezo1 channel, provides a potential solution to intensify the effects of LMHF vibration. This study aims to investigate the effects of combined treatment (Yoda1 and LMHF vibration) in regulating osteoclastogenesis and breast cancer cell migration. We confirmed that combining LMHF vibration and Yoda1 reduces the formation of osteoclasts and further inhibits the migration of MDA-MB-231 breast cancer cells. Our data supported the novel strategy to regulate cancer cell migration for high-risk patients. Low-magnitude (≤1 g) high-frequency (≥30 Hz) (LMHF) vibration has been shown to enhance bone mineral density. However, its regulation in breast cancer bone metastasis remains controversial for breast cancer patients and elder populations. Yoda1, an activator of the mechanosensitive Piezo1 channel, could potentially intensify the effect of LMHF vibration by enhancing the mechanoresponse of osteocytes, the major mechanosensory bone cells with high expression of Piezo1. In this study, we treated osteocytes with mono- (Yoda1 only or vibration only) or combined treatment (Yoda1 and LMHF vibration) and examined the further regulation of osteoclasts and breast cancer cells through the conditioned medium. Moreover, we studied the effects of combined treatment on breast cancer cells in regulation of osteocytes. Combined treatment on osteocytes showed beneficial effects, including increasing the nuclear translocation of Yes-associated protein (YAP) in osteocytes (488.0%, p < 0.0001), suppressing osteoclastogenesis (34.3%, p = 0.004), and further reducing migration of MDA-MB-231 (15.1%, p = 0.02) but not Py8119 breast cancer cells (4.2%, p = 0.66). Finally, MDA-MB-231 breast cancer cells subjected to the combined treatment decreased the percentage of apoptotic osteocytes (34.5%, p = 0.04) but did not affect the intracellular calcium influx. This study showed the potential of stimulating Piezo1 in enhancing the mechanoresponse of osteocytes to LMHF vibration and further suppressing breast cancer migration via osteoclasts.
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