Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544.
Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202.
Cold Spring Harb Perspect Med. 2018 Jun 1;8(6):a031252. doi: 10.1101/cshperspect.a031252.
Bone metastasis, or the development of secondary tumors within the bone of cancer patients, is a debilitating and incurable disease. Despite its morbidity, the biology of bone metastasis represents one of the most complex and intriguing of all oncogenic processes. This complexity derives from the intricately organized bone microenvironment in which the various stages of hematopoiesis, osteogenesis, and osteolysis are jointly regulated but spatially restricted. Disseminated tumor cells (DTCs) from various common malignancies such as breast, prostate, lung, and kidney cancers or myeloma are uniquely primed to subvert these endogenous bone stromal elements to grow into pathological osteolytic or osteoblastic lesions. This colonization process can be separated into three key steps: seeding, dormancy, and outgrowth. Targeting the processes of dormancy and initial outgrowth offers the most therapeutic promise. Here, we discuss the concepts of the bone metastasis niche, from controlling tumor-cell survival to growth into clinically detectable disease.
骨转移，即癌症患者骨骼内的继发性肿瘤的发展，是一种使人虚弱且无法治愈的疾病。尽管其发病率很高，但骨转移的生物学特性代表了所有致癌过程中最复杂和最有趣的一个。这种复杂性源自于组织复杂的骨微环境，其中造血、成骨和溶骨的各个阶段共同受到调节，但空间上受到限制。来自各种常见恶性肿瘤（如乳腺癌、前列腺癌、肺癌和肾癌或骨髓瘤）的播散性肿瘤细胞（DTC）被特别激活，以破坏这些内源性骨基质成分，生长为病理性溶骨性或成骨性病变。这个定植过程可以分为三个关键步骤：播种、休眠和生长。靶向休眠和初始生长的过程提供了最有希望的治疗方法。在这里，我们讨论了骨转移龛的概念，从控制肿瘤细胞的存活到生长为临床可检测的疾病。
