School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Engineering Research Center of Shanghai Colleges for TCM New Drug Discovery, Shanghai, 201203, China.
J Exp Clin Cancer Res. 2022 Oct 28;41(1):316. doi: 10.1186/s13046-022-02520-0.
Bone metastasis occurs when tumour cells dissociate from primary tumours, enter the circulation (circulating tumour cells, CTCs), and colonize sites in bone (disseminated tumour cells, DTCs). The bone marrow seems to be a particularly dormancy-inducing environment for DTCs, yet the mechanisms of dormancy initiation, reactivation, and interaction within the bone marrow have to be elucidated. Intriguingly, some evidence has suggested that dormancy is a reversible state that is switched 'on' or 'off' depending on the presence of various bone marrow resident cells, particularly osteoclasts and osteoblasts. It has become clear that these two cells contribute to regulating dormant tumour cells in bone both directly (interaction) and indirectly (secreted factors). The involved mechanisms include TGFβ signalling, the Wnt signalling axis, the Notch2 pathway, etc. There is no detailed review that specifically focuses on ascertaining the dynamic interactions between tumour cell dormancy and bone remodelling. In addition, we highlighted the roles of inflammatory cytokines during this 'cell-to-cell' communication. We also discussed the potential clinical relevance of remodelling the bone marrow niche in controlling dormant tumour cells. Understanding the unique role of osteoclasts and osteoblasts in regulating tumour dormancy in bone marrow will provide new insight into preventing and treating tumour bone metastasis.
当肿瘤细胞从原发性肿瘤中分离出来，进入循环系统（循环肿瘤细胞，CTC），并在骨骼中定植（播散性肿瘤细胞，DTC）时，就会发生骨转移。骨髓似乎对 DTC 具有特别的休眠诱导环境，但休眠的起始、重新激活和在骨髓内相互作用的机制仍需阐明。有趣的是，有一些证据表明，休眠是一种可逆的状态，可以根据各种骨髓常驻细胞（特别是破骨细胞和成骨细胞）的存在而“开启”或“关闭”。很明显，这两种细胞通过直接（相互作用）和间接（分泌因子）的方式，有助于调节骨骼中的休眠肿瘤细胞。涉及的机制包括 TGFβ 信号通路、Wnt 信号轴、Notch2 通路等。目前还没有专门针对确定肿瘤细胞休眠与骨重塑之间动态相互作用的详细综述。此外，我们强调了在这种“细胞间”通讯过程中炎症细胞因子的作用。我们还讨论了重塑骨髓龛以控制休眠肿瘤细胞的潜在临床相关性。了解破骨细胞和成骨细胞在调节骨髓中肿瘤休眠方面的独特作用，将为预防和治疗肿瘤骨转移提供新的见解。
