Jinnah Alexander H, Zacks Benjamin C, Gwam Chukwuweike U, Kerr Bethany A
Department of Orthopaedic Surgery, Wake Forest School of Medicine, Winston Salem, NC 27157, USA.
Department of Cancer Biology, Wake Forest School of Medicine, Winston Salem, NC 27157, USA.
Cancers (Basel). 2018 Jun 1;10(6):176. doi: 10.3390/cancers10060176.
Metastasis is the leading cause of cancer-related death and drives patient morbidity as well as healthcare costs. Bone is the primary site of metastasis for several cancers-breast and prostate cancers in particular. Efforts to treat bone metastases have been stymied by a lack of models to study the progression, cellular players, and signaling pathways driving bone metastasis. In this review, we examine newly described and classic models of bone metastasis. Through the use of current in vivo, microfluidic, and in silico computational bone metastasis models we may eventually understand how cells escape the primary tumor and how these circulating tumor cells then home to and colonize the bone marrow. Further, future models may uncover how cells enter and then escape dormancy to develop into overt metastases. Recreating the metastatic process will lead to the discovery of therapeutic targets for disrupting and treating bone metastasis.
转移是癌症相关死亡的主要原因,会导致患者发病并增加医疗成本。骨是几种癌症(尤其是乳腺癌和前列腺癌)转移的主要部位。由于缺乏用于研究骨转移进展、相关细胞及驱动骨转移的信号通路的模型,治疗骨转移的努力一直受到阻碍。在本综述中,我们研究了新描述的和经典的骨转移模型。通过使用当前的体内、微流控和计算机模拟骨转移模型,我们最终可能会了解细胞如何逃离原发肿瘤,以及这些循环肿瘤细胞如何归巢并定植于骨髓。此外,未来的模型可能会揭示细胞如何进入并随后逃离休眠状态,发展为明显的转移灶。重现转移过程将有助于发现破坏和治疗骨转移的治疗靶点。