Department of Surgery, St. Vincent's Hospital, University of Melbourne, 29 Regent St., Fitzroy, Melbourne, Australia 3065.
Cancer Metastasis Rev. 2012 Dec;31(3-4):469-78. doi: 10.1007/s10555-012-9377-5.
As yet, there is no cure for metastatic breast cancer. Historically, considerable research effort has been concentrated on understanding the processes of metastasis, how a primary tumour locally invades and systemically disseminates using the phenotypic switching mechanism of epithelial to mesenchymal transition (EMT); however, much less is understood about how metastases are then formed. Breast cancer metastases often look (and may even function) as 'normal' breast tissue, a bizarre observation against the backdrop of the organ structure of the lung, liver, bone or brain. Mesenchymal to epithelial transition (MET), the opposite of EMT, has been proposed as a mechanism for establishment of the metastatic neoplasm, leading to questions such as: Can MET be clearly demonstrated in vivo? What factors cause this phenotypic switch within the cancer cell? Are these signals/factors derived from the metastatic site (soil) or expressed by the cancer cells themselves (seed)? How do the cancer cells then grow into a detectable secondary tumour and further disseminate? And finally--Can we design and develop therapies that may combat this dissemination switch? This review aims to address these important questions by evaluating long-standing paradigms and novel emerging concepts in the field of epithelial mesencyhmal plasticity.
目前，转移性乳腺癌还无法治愈。从历史上看，大量的研究工作集中在理解转移的过程上，即原发性肿瘤如何通过上皮-间充质转化（EMT）的表型转换机制在局部侵袭和系统扩散；然而，人们对转移是如何形成的知之甚少。乳腺癌转移通常看起来（甚至可能发挥作用）像“正常”的乳腺组织，这一奇特的观察结果与肺、肝、骨或脑等器官结构形成鲜明对比。间充质上皮转化（MET），EMT 的相反过程，被提出作为转移瘤形成的机制，引发了一些问题，例如：MET 能否在体内得到明确证明？哪些因素导致癌细胞发生这种表型转换？这些信号/因素是来自转移部位（土壤）还是由癌细胞本身表达（种子）？癌细胞如何进一步生长为可检测的次级肿瘤并进一步扩散？最后，我们能否设计和开发可能对抗这种扩散开关的治疗方法？本综述旨在通过评估上皮间充质可塑性领域的长期存在的范例和新兴概念来解决这些重要问题。
