文章：

骨转移：邻里关系的重要性

Bone metastasis: the importance of the neighbourhood

原文发布日期：2016-05-25

DOI: 10.1038/nrc.2016.44

类型: Review Article

开放获取: 否

要点：

1. Several tumours either develop in the skeleton, such as multiple myeloma, or metastasize to bone, such as breast and prostate cancers.
2. The skeleton provides a unique microenvironment that supports the development of these tumours, although the nature of this microenvironment has until recently been poorly defined.
3. Our understanding of the early, crucial events of tumour cell colonization, survival and dormancy, and reactivation of dormant cancer cells has been limited. However, progress in single cell imaging and molecular techniques has provided new insights.
4. Tumour cell dormancy in the skeleton is induced by interactions with specific cells in the local bone microenvironment. Cells of the osteoblast lineage, present on the endosteal bone surface, provide a supportive niche to keep tumour cells in a dormant state.
5. Reactivation of dormant tumour cells is mediated by extrinsic changes in the bone microenvironment. Osteoclasts, by remodelling the endosteal bone surface, represent one mechanism by which dormant cells can be reactivated.
6. Our improved understanding of the control of tumour dormancy in the skeleton has revealed new therapeutic opportunities. These include using bone-active drugs to promote long-term tumour cell dormancy, or conversely, promoting reactivation and targeting dormant cells to eradicate them and 'cure' tumours that develop in bone.

要点翻译：

1. 多种肿瘤或原发于骨骼，如多发性骨髓瘤，或转移至骨骼，如乳腺癌和前列腺癌。
2. 骨骼提供了一个独特的微环境，支持这些肿瘤的发展，尽管直到最近，这种微环境的性质仍不明确。
3. 我们对肿瘤细胞定植、存活、休眠以及休眠癌细胞再激活这些早期关键事件的理解一直有限。然而，单细胞成像和分子技术的进步提供了新的见解。
4. 骨骼中肿瘤细胞的休眠是由与局部骨微环境中特定细胞的相互作用诱导的。位于骨内膜表面的成骨细胞谱系细胞提供了一个支持性微环境，使肿瘤细胞保持休眠状态。
5. 休眠肿瘤细胞的再激活是由骨微环境的外部变化介导的。破骨细胞通过重塑骨内膜表面，代表了休眠细胞被重新激活的一种机制。
6. 我们对骨骼中肿瘤休眠控制机制的深入理解揭示了新的治疗机会。这些包括使用骨活性药物促进肿瘤细胞长期休眠，或者相反，促进再激活并靶向休眠细胞以根除它们，从而“治愈”在骨骼中发展的肿瘤。

英文摘要：

During the past decade preclinical studies have defined many of the mechanisms used by tumours to hijack the skeleton and promote bone metastasis. This has led to the development and widespread clinical use of bone-targeted drugs to prevent skeletal-related events. This understanding has also identified a critical dependency between colonizing tumour cells and the cells of bone. This is particularly important when tumour cells first arrive in bone, adapt to their new microenvironment and enter a long-lived dormant state. In this Review, we discuss the role of different bone cell types in supporting disseminated tumour cell dormancy and reactivation, and highlight the new opportunities this provides for targeting the bone microenvironment to control dormancy and bone metastasis.

摘要翻译： 

在过去十年中，临床前研究已阐明肿瘤劫持骨骼并促进骨转移的多种机制。这促使骨靶向药物得以开发并广泛应用于临床，以预防骨相关事件。这一认识也揭示了定植肿瘤细胞与骨细胞之间关键的依赖关系，尤其在肿瘤细胞初抵骨骼、适应新微环境并进入长期休眠状态时尤为重要。本文综述了不同骨细胞类型在支持播散性肿瘤细胞休眠与再激活中的作用，并强调了由此带来的新机遇——通过靶向骨微环境来控制休眠与骨转移。

原文链接：

Bone metastasis: the importance of the neighbourhood