Bone frequently serves as a metastatic site for breast and prostate cancers. Given the potential of low-intensity vibration (LIV) to increase bone health and reduce cancer risk, this study investigated the impact of LIV on cancer cells, as well as noncancer cells such as lymphocytes and peripheral blood mononuclear cells (PBMCs). The results revealed that LIV exposure not only suppressed cancer cell migration but also triggered the generation of induced tumor-suppressing (iTS) cells. Conditioned medium (CM) derived from LIV-treated PBMCs shrank freshly isolated breast and prostate cancer tissues, and when CM was combined with a chemotherapeutic agent, additional antitumor effects were observed. Notably, iTS cell-derived CM hindered the maturation of the receptor activator of nuclear factor-kappa B ligand (RANKL)-stimulated bone-resorbing osteoclasts while promoting the differentiation of bone-forming osteoblasts. Intriguingly, the anticancer effects induced by LIV were replicated by simply shaking a cell-containing tube with a regular tube shaker. Using mass spectrometry-based proteomics, this study revealed enrichment of tumor-suppressing proteins, including enolase 1, moesin (MSN), and aldolase A (ALDOA), which are commonly found in oncogene-activated iTS cells, in LIV-induced CM. Sad1 and UNC-84 domain containing 1 (SUN1), a core component of the linker of the nucleoskeleton and cytoskeleton (LINC) complex, exhibited heightened expression, notably enhancing the response of lymphocytes to LIV. An ex vivo bone cancer model further demonstrated the potent anticancer effects of lymphocyte-derived CM. In conclusion, this study underscores the pivotal role of LIV in preventing bone loss in the tumor microenvironment.

中文翻译：

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对低强度振动产生诱导肿瘤抑制细胞和调节骨微环境的治疗见解


骨骼经常是乳腺癌和前列腺癌的转移部位。鉴于低强度振动 （LIV） 有可能增加骨骼健康和降低癌症风险，本研究调查了 LIV 对癌细胞以及淋巴细胞和外周血单核细胞 （PBMC） 等非癌细胞的影响。结果显示，LIV 暴露不仅抑制癌细胞迁移，还触发诱导肿瘤抑制 （iTS） 细胞的产生。源自 LIV 处理的 PBMC 的条件培养基 （CM） 使新鲜分离的乳腺癌和前列腺癌组织缩小，当 CM 与化疗药物联合使用时，观察到额外的抗肿瘤作用。值得注意的是，iTS 细胞来源的 CM 阻碍了核因子-κ B 配体 （RANKL） 刺激的骨吸收破骨细胞受体激活剂的成熟，同时促进了成骨成骨细胞的分化。有趣的是，LIV 诱导的抗癌作用是通过简单地用普通摇床摇动含细胞的试管来复制的。使用基于质谱的蛋白质组学，本研究揭示了在 LIV 诱导的 CM 中肿瘤抑制蛋白的富集，包括烯醇化酶 1、moesin （MSN） 和醛缩酶 A （ALDOA），这些蛋白常见于癌基因激活的 iTS 细胞中。Sad1 和 UNC-84 结构域包含 1 （SUN1） 是核骨架和细胞骨架 （LINC） 复合物接头的核心成分，表现出高表达，显着增强淋巴细胞对 LIV 的反应。离体骨癌模型进一步证明了淋巴细胞来源的 CM 具有强大的抗癌作用。总之，本研究强调了 LIV 在预防肿瘤微环境中骨质流失方面的关键作用。