Calero Alba, Fernández-Marcelo Tamara, Sury Paulina, de Lucas Beatriz, Gálvez Beatriz G
Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Universidad Complutense de Madrid (UCM), Madrid, Spain.
Faculty of Sports Sciences, Universidad Europea de Madrid, Madrid, Spain.
Cancer Cell Int. 2025 Jun 14;25(1):212. doi: 10.1186/s12935-025-03854-3.
Ultrasound is considered a safe and non-invasive tool in regenerative medicine. In particular, low-intensity pulsed ultrasound (LIPUS) has been used in the clinic for more than twenty years for applications in bone healing. It has been demonstrated to be an effective tool to treat different chronic diseases. We sought to evaluate the effects produced by LIPUS on the properties of human breast cancer stem cells (bCSCs).
Cells were stimulated using a traditional ultrasound device with the following parameters: 0.05 W/cm with 10% duty cycle, frequency of 3 MHz and 8 pulses.
At the parameters used, the ultrasound did not directly affect bCSC proliferation, with no evident changes in morphology. In contrast, the ultrasound protocol affected the migration and invasion ability of bCSCs, limiting their capacity to advance while a major affection was detected on their angiogenic properties. LIPUS-treated bCSCs were unable to transform into aggressive metastatic cancer cells, by decreasing their migration and invasion capacity as well as vessel formation. Finally, RNA-seq analysis revealed major changes in gene expression, with 676 differentially expressed genes after LIPUS stimulation, 578 upregulated and 98 downregulated.
Overall, these results highlight the potential of LIPUS as a promising non-invasive therapy to target bCSCs and attenuate its capacity to drive migration, invasion, angiogenesis and, ultimately, tumor malignancy. Besides, the ability of LIPUS to modulate gene expression points out its capacity to broadly influence the cellular transcriptome. Therefore, the application of LIPUS as an antitumor therapeutic agent targeting bCSCs may offer a promising new approach to treat cancer. In vivo functional experiments will determine in the future the relevance of LIPUS application for the development of metastasis.
超声被认为是再生医学中一种安全且无创的工具。特别是，低强度脉冲超声（LIPUS）已在临床上用于骨愈合应用二十多年。它已被证明是治疗不同慢性疾病的有效工具。我们试图评估LIPUS对人乳腺癌干细胞（bCSCs）特性产生的影响。
使用传统超声设备以以下参数刺激细胞：功率密度0.05W/cm，占空比10%，频率3MHz，脉冲数8个。
在所使用的参数下，超声并未直接影响bCSC的增殖，细胞形态无明显变化。相比之下，超声方案影响了bCSCs的迁移和侵袭能力，限制了它们的前进能力，同时在其血管生成特性上检测到较大影响。经LIPUS处理的bCSCs无法转变为侵袭性转移性癌细胞，其迁移、侵袭能力以及血管形成能力均降低。最后，RNA测序分析揭示了基因表达的重大变化，LIPUS刺激后有676个差异表达基因，其中578个上调，98个下调。
总体而言，这些结果突出了LIPUS作为一种有前景的非侵入性疗法靶向bCSCs并减弱其驱动迁移、侵袭、血管生成以及最终肿瘤恶性程度的能力的潜力。此外，LIPUS调节基因表达的能力指出了其广泛影响细胞转录组的能力。因此，将LIPUS作为靶向bCSCs的抗肿瘤治疗剂应用可能为癌症治疗提供一种有前景的新方法。未来的体内功能实验将确定LIPUS应用对转移发展的相关性。
