Brown Janet E, Westbrook Jules A, Wood Steven L
Department of Oncology & Metabolism, Academic Unit of Clinical Oncology, The University of Sheffield, Sheffield, UK.
Cancer Inform. 2019 Aug 26;18:1176935119866842. doi: 10.1177/1176935119866842. eCollection 2019.
Metastasis to bone occurs in over 70% of patients with advanced breast cancer resulting in skeletal complications, including pathological fractures, hypercalcaemia, and bone pain. Significant advances have been made in the treatment of bone metastases, including the use of antiresorptive drugs, such as bisphosphonates, as well as antibody-based therapies targeting key signalling intermediates within the process of cancer-mediated bone destruction. Despite these advances, treatment is not without side effects, including osteonecrosis of the jaw therefore biomarkers predictive of which patients are at high risk of developing bone spread are required to enable personalized medicine initiatives within this important disease area. We used proteomic analysis to compare the protein expression within (1) a parental triple negative human breast cancer cell line, (2) a fully bone homing cell line and (3) a lung homing cell line. The bone and lung homing cell-lines were derived by intra-cardiac injection of fluorescently labelled cells within immune-compromised mice. Proteomics identified Dedicator of Cytokinesis 4 as a biomarker predictive of bone spread, and this finding was further supported by the observation that high levels of Dedicator of Cytokinesis 4 within primary breast tumours were predictive of breast cancer spread to bone. Here, we provide an overview of this study and put the findings into context.
超过70%的晚期乳腺癌患者会发生骨转移,从而导致骨骼并发症,包括病理性骨折、高钙血症和骨痛。在骨转移的治疗方面已经取得了重大进展,包括使用抗吸收药物,如双膦酸盐,以及针对癌症介导的骨破坏过程中关键信号中间体的基于抗体的疗法。尽管有这些进展,但治疗并非没有副作用,包括颌骨坏死,因此需要能够预测哪些患者发生骨转移风险较高的生物标志物,以便在这个重要的疾病领域开展个性化医疗方案。我们使用蛋白质组学分析来比较(1)亲本三阴性人乳腺癌细胞系、(2)完全归巢于骨的细胞系和(3)归巢于肺的细胞系中的蛋白质表达。骨归巢和肺归巢细胞系是通过在免疫受损小鼠心内注射荧光标记细胞获得的。蛋白质组学鉴定出细胞分裂专用蛋白4作为预测骨转移的生物标志物,原发性乳腺肿瘤中细胞分裂专用蛋白4水平较高可预测乳腺癌转移至骨这一观察结果进一步支持了这一发现。在此,我们概述了这项研究并阐述了研究结果。