Smith James T, Chai Ryan C
Bone Biology Lab, Cancer Plasticity and Dormancy Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Australia.
J Bone Oncol. 2024 Jul 6;47:100621. doi: 10.1016/j.jbo.2024.100621. eCollection 2024 Aug.
Secondary metastases, accounting for 90 % of cancer-related deaths, pose a formidable challenge in cancer treatment, with bone being a prevalent site. Importantly, tumours may relapse, often in the skeleton even after successful eradication of the primary tumour, indicating that tumour cells may lay dormant within bone for extended periods of time. This review summarises recent findings in the mechanisms underlying tumour cell dormancy and the role of bone cells in this process. Hematopoietic stem cell (HSC) niches in bone provide a model for understanding regulatory microenvironments. Dormant tumour cells have been shown to exploit similar niches, with evidence suggesting interactions with osteoblast-lineage cells and other stromal cells via CXCL12-CXCR4, integrins, and TAM receptor signalling, especially through GAS6-AXL, led to dormancy, with exit of dormancy potentially regulated by osteoclastic bone resorption and neuronal signalling. A comprehensive understanding of dormant tumour cell niches and their regulatory mechanisms is essential for developing targeted therapies, a critical step towards eradicating metastatic tumours and stopping disease relapse.
继发性转移占癌症相关死亡的90%，在癌症治疗中构成了巨大挑战，骨骼是常见的转移部位。重要的是，肿瘤可能复发，即使在成功根除原发性肿瘤后，也常常在骨骼中复发，这表明肿瘤细胞可能在骨骼中长时间处于休眠状态。本综述总结了肿瘤细胞休眠机制以及骨细胞在此过程中的作用的最新研究发现。骨髓中的造血干细胞（HSC）微环境为理解调节性微环境提供了一个模型。已证明休眠肿瘤细胞利用类似的微环境，有证据表明通过CXCL12 - CXCR4、整合素和TAM受体信号通路，特别是通过GAS6 - AXL与成骨细胞系细胞和其他基质细胞相互作用导致休眠，而休眠的解除可能受破骨细胞骨吸收和神经信号调节。全面了解休眠肿瘤细胞微环境及其调节机制对于开发靶向治疗至关重要，这是根除转移性肿瘤和阻止疾病复发的关键一步。
