Department of Chemical and Biomolecular Engineering, Russ College of Engineering and Technology, Ohio University Athens, OH, USA.
Front Oncol. 2012 Aug 20;2:103. doi: 10.3389/fonc.2012.00103. eCollection 2012.
Although significant progress has been made in the fight against cancer, successful treatment strategies have yet to be developed to combat those tumors that have metastasized to distant organs. Poor characterization of the molecular mechanisms of cancer spread is a major impediment to designing predictive diagnostics and effective clinical interventions against late stage disease. In hematogenous metastasis, it is widely suspected that circulating tumor cells (CTCs) express specific adhesion molecules that actively initiate contact with the vascular endothelium lining the vessel walls of the target organ. This "tethering" is mediated by ligands expressed by CTCs that bind to E-selectin expressed by endothelial cells. However, it is currently unknown whether expression of functional E-selectin ligands on CTCs is related to cancer stem cell regulatory or maintenance pathways, particularly epithelial-to-mesenchymal transition and the reverse, mesenchymal-to-epithelial transition. In this hypothesis and theory article, we explore the potential roles of these mechanisms on the dynamic regulation of selectin ligands mediating CTC trafficking during metastasis.
尽管在抗癌方面已经取得了重大进展，但仍未开发出成功的治疗策略来对抗那些已经转移到远处器官的肿瘤。癌症扩散的分子机制描述不佳是设计预测性诊断和针对晚期疾病的有效临床干预措施的主要障碍。在血源性转移中，人们普遍怀疑循环肿瘤细胞 (CTC) 表达特定的粘附分子，这些分子可主动与靶器官血管壁内皮细胞接触。这种“连接”是由 CTC 表达的配体介导的，这些配体与内皮细胞表达的 E-选择素结合。然而，目前尚不清楚 CTC 上功能性 E-选择素配体的表达是否与癌症干细胞调节或维持途径有关，特别是上皮-间充质转化和相反的间充质-上皮转化。在这篇假说和理论文章中，我们探讨了这些机制在选择素配体动态调节中的潜在作用，这些配体介导转移过程中的 CTC 迁移。
