General Practice Centre, The Seventh Affiliated Hospital, Southern Medical University, Foshan, China.
Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
Elife. 2024 Mar 28;12:RP89613. doi: 10.7554/eLife.89613.
Although preclinical and clinical studies have shown that exercise can inhibit bone metastasis progression, the mechanism remains poorly understood. Here, we found that non-small cell lung cancer (NSCLC) cells adjacent to bone tissue had a much lower proliferative capacity than the surrounding tumor cells in patients and mice. Subsequently, it was demonstrated that osteocytes, sensing mechanical stimulation generated by exercise, inhibit NSCLC cell proliferation and sustain the dormancy thereof by releasing small extracellular vesicles with tumor suppressor micro-RNAs, such as miR-99b-3p. Furthermore, we evaluated the effects of mechanical loading and treadmill exercise on the bone metastasis progression of NSCLC in mice. As expected, mechanical loading of the tibia inhibited the bone metastasis progression of NSCLC. Notably, bone metastasis progression of NSCLC was inhibited by moderate exercise, and combinations with zoledronic acid had additive effects. Moreover, exercise preconditioning effectively suppressed bone metastasis progression. This study significantly advances the understanding of the mechanism underlying exercise-afforded protection against bone metastasis progression.
虽然临床前和临床研究表明，运动可以抑制骨转移的进展，但其中的机制仍知之甚少。在这里，我们发现，与骨组织相邻的非小细胞肺癌（NSCLC）细胞的增殖能力比患者和小鼠周围的肿瘤细胞低得多。随后，研究表明，成骨细胞通过释放含有肿瘤抑制 micro-RNAs（如 miR-99b-3p）的小细胞外囊泡，感知运动产生的机械刺激，抑制 NSCLC 细胞的增殖并维持其休眠。此外，我们评估了机械加载和跑步机运动对小鼠 NSCLC 骨转移进展的影响。正如预期的那样，胫骨的机械加载抑制了 NSCLC 的骨转移进展。值得注意的是，中等强度的运动抑制了 NSCLC 的骨转移进展，与唑来膦酸联合使用具有相加作用。此外，运动预处理能有效抑制骨转移的进展。这项研究显著提高了我们对运动抑制骨转移进展的保护机制的理解。
