F-actin(filamentous actin)has been shown to be sensitive to mechanical stimuli and play critical roles in cell attachment,migration,and cancer metastasis,but there are very limited ways to perturb F-actin dynamics wit...F-actin(filamentous actin)has been shown to be sensitive to mechanical stimuli and play critical roles in cell attachment,migration,and cancer metastasis,but there are very limited ways to perturb F-actin dynamics with low cell toxicity.Magnetic field is a noninvasive and reversible physical tool that can easily penetrate cells and human bodies.Here,we show that 0.1/0.4-T 4.2-Hz moderate-intensity low-frequency rotating magnetic field-induced electric field could directly decrease F-actin formation in vitro and in vivo,which results in decreased breast cancer cell migration,invasion,and attachment.Moreover,lowfrequency rotating magnetic fields generated significantly different effects on F-actin in breast cancer vs.noncancerous cells,including F-actin number and their recovery after magnetic field retrieval.Using an intermittent treatment modality,low-frequency rotating magnetic fields could significantly reduce mouse breast cancer metastasis,prolong mouse survival by 31.5 to 46.0%(P<0.0001),and improve their overall physical condition.Therefore,our work demonstrates that low-frequency rotating magnetic fields not only can be used as a research tool to perturb F-actin but also can inhibit breast cancer metastasis through F-actin modulation while having minimum effects on normal cells,which reveals their potential to be developed as temporal-controlled,noninvasive,and high-penetration physical treatments for metastatic cancer.展开更多
基金This work was supported by the National Natural Science Foundation of China(U21A20148,52007185,and 31900506)International Partnership Program of Chinese Academy of Sciences(116134KYSB20210052)+4 种基金the CASHIPS Director’s Fund(2021YZGH04,BJPY2021A06,and YZJJZX202014)A portion of this work was supported by the High Magnetic Field Laboratory of Anhui Province(AHHMFX-2021-05)the Heye Health Technology Chong Ming Project under award number(HYCMP2021010)Operational Programme Research,Development and Education as well as financed by the European Structural and Investment Funds and the Czech Ministry of Education,Youth and Sports through Project No.SOLID21-CZ.02.1.01/0.0/0.0/16_019/0000760the CAS president’s international fellowship initiative(PIFI)grant(2022VMA0009)。
文摘F-actin(filamentous actin)has been shown to be sensitive to mechanical stimuli and play critical roles in cell attachment,migration,and cancer metastasis,but there are very limited ways to perturb F-actin dynamics with low cell toxicity.Magnetic field is a noninvasive and reversible physical tool that can easily penetrate cells and human bodies.Here,we show that 0.1/0.4-T 4.2-Hz moderate-intensity low-frequency rotating magnetic field-induced electric field could directly decrease F-actin formation in vitro and in vivo,which results in decreased breast cancer cell migration,invasion,and attachment.Moreover,lowfrequency rotating magnetic fields generated significantly different effects on F-actin in breast cancer vs.noncancerous cells,including F-actin number and their recovery after magnetic field retrieval.Using an intermittent treatment modality,low-frequency rotating magnetic fields could significantly reduce mouse breast cancer metastasis,prolong mouse survival by 31.5 to 46.0%(P<0.0001),and improve their overall physical condition.Therefore,our work demonstrates that low-frequency rotating magnetic fields not only can be used as a research tool to perturb F-actin but also can inhibit breast cancer metastasis through F-actin modulation while having minimum effects on normal cells,which reveals their potential to be developed as temporal-controlled,noninvasive,and high-penetration physical treatments for metastatic cancer.
