Division of Clinical Pharmacology, Department of Medicine, Vanderbilt Center for Bone Biology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, 77843, USA.
Calcif Tissue Int. 2018 Feb;102(2):141-151. doi: 10.1007/s00223-017-0362-4. Epub 2017 Nov 14.
Breast cancer bone metastasis develops as the result of a series of complex interactions between tumor cells, bone marrow cells, and resident bone cells. The net effect of these interactions are the disruption of normal bone homeostasis, often with significantly increased osteoclast and osteoblast activity, which has provided a rational target for controlling tumor progression, with little or no emphasis on tumor eradication. Indeed, the clinical course of metastatic breast cancer is relatively long, with patients likely to experience sequential skeletal-related events (SREs), often over lengthy periods of time, even up to decades. These SREs include bone pain, fractures, and spinal cord compression, all of which may profoundly impair a patient's quality-of-life. Our understanding of the contributions of the host bone and bone marrow cells to the control of tumor progression has grown over the years, yet the focus of virtually all available treatments remains on the control of resident bone cells, primarily osteoclasts. In this perspective, our focus is to move away from the current emphasis on the control of bone cells and focus our attention on the hallmarks of bone metastatic tumor cells and how these differ from primary tumor cells and normal host cells. In our opinion, there remains a largely unmet medical need to develop and utilize therapies that impede metastatic tumor cells while sparing normal host bone and bone marrow cells. This perspective examines the impact of metastatic tumor cells on the bone microenvironment and proposes potential new directions for uncovering the important mechanisms driving metastatic progression in bone based on the hallmarks of bone metastasis.
乳腺癌骨转移是肿瘤细胞、骨髓细胞和固有骨细胞之间一系列复杂相互作用的结果。这些相互作用的净效应是破坏正常的骨稳态，通常伴有显著增加的破骨细胞和成骨细胞活性，这为控制肿瘤进展提供了合理的靶点，几乎没有或没有强调肿瘤的根除。事实上，转移性乳腺癌的临床过程相对较长，患者可能会经历连续的骨骼相关事件（SREs），通常持续很长时间，甚至长达几十年。这些 SREs 包括骨痛、骨折和脊髓压迫，所有这些都可能严重损害患者的生活质量。我们对宿主骨和骨髓细胞对控制肿瘤进展的贡献的理解多年来一直在增长，但实际上几乎所有可用治疗方法的重点仍然是控制固有骨细胞，主要是破骨细胞。在这篇观点文章中，我们的重点是不再强调控制骨细胞，而是将注意力集中在骨转移肿瘤细胞的特征上，以及这些特征与原发性肿瘤细胞和正常宿主细胞的不同之处。我们认为，仍然存在着大量未满足的医疗需求，需要开发和利用能够阻止转移性肿瘤细胞而不损伤正常宿主骨和骨髓细胞的治疗方法。这篇观点文章探讨了转移性肿瘤细胞对骨微环境的影响，并基于骨转移的特征，提出了揭示骨转移进展中重要机制的潜在新方向。
