Department of Pathology, Josephine Nefkens Institute, Erasmus MC, Rotterdam, The Netherlands.
Eur J Cancer. 2010 May;46(7):1198-203. doi: 10.1016/j.ejca.2010.02.030. Epub 2010 Mar 18.
The transient and dynamic nature of cancer cells that underlie metastasis cannot only be explained by the progressive accumulation of irreversible genetic changes occurring in the primary tumour. The capacity of cells to switch between different cellular identities, as in epithelial to mesenchymal (EMT) and mesenchymal to epithelial transitions (MET), allows them to respond to different cellular environments, thus efficiently disseminating from the primary mass to eventually colonise distant organs. These more dynamic stem-like cancer cells are earmarked by the ability to self-renew and de-/re-differentiate, and eventually recapitulate the heterogeneous composition of the primary tumour in a distant organ site. This dynamic concept of metastasis has profound consequences and implications for cancer diagnostics, prognostics and therapy. Many of the characteristics that define stem cells, like dormancy, active DNA repair, the expression of several drug transporters, and resistance to apoptosis may underlie the capacity of migrating cancer cells to survive conventional therapeutic protocols based on genotoxic agents targeting active proliferating cells. Accordingly, signal transduction pathways that regulate the balance between self-renewal and differentiation are likely to represent future targets in the development of tailor-made intervention strategies. Also, specific stem cell features, such as the capacity to migrate to diseased areas (pathotropism), open novel avenues towards the development of cell vehicles capable of tracking and delivering anti-cancer compounds to disseminated metastatic lesions.
癌症转移的基础是癌细胞的瞬态和动态特性，这不仅可以用原发性肿瘤中发生的不可逆转的遗传变化的逐渐积累来解释。细胞在不同细胞状态之间转换的能力，如上皮到间充质（EMT）和间充质到上皮（MET）的转变，使它们能够对不同的细胞环境做出反应，从而有效地从原发性肿瘤中扩散，最终在远处器官定植。这些更具动态特性的肿瘤干细胞具有自我更新和去/再分化的能力，并最终在远处器官部位重现原发性肿瘤的异质性组成。这种转移的动态概念对癌症的诊断、预后和治疗具有深远的影响和意义。许多定义干细胞的特征，如休眠、主动 DNA 修复、多种药物转运蛋白的表达以及对细胞凋亡的抵抗，可能是迁移的癌细胞能够在基于针对活跃增殖细胞的遗传毒性药物的常规治疗方案中存活的原因。因此，调节自我更新和分化之间平衡的信号转导途径可能代表着未来针对个体化干预策略的开发的潜在靶点。此外，特定的干细胞特征，如迁移到病变部位的能力（归巢性），为开发能够追踪和向扩散的转移性病变输送抗癌化合物的细胞载体开辟了新途径。
