转移:组织力学与肿瘤细胞可塑性之间的串扰。
Metastasis: crosstalk between tissue mechanics and tumour cell plasticity.
机构信息
Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands.
出版信息
Br J Cancer. 2021 Jan;124(1):49-57. doi: 10.1038/s41416-020-01150-7. Epub 2020 Nov 18.
Despite the fact that different genetic programmes drive metastasis of solid tumours, the ultimate outcome is the same: tumour cells are empowered to pass a series of physical hurdles to escape the primary tumour and disseminate to other organs. Epithelial-to-mesenchymal transition (EMT) has been proposed to drive the detachment of individual cells from primary tumour masses and facilitate the subsequent establishment of metastases in distant organs. However, this concept has been challenged by observations from pathologists and from studies in animal models, in which partial and transient acquisition of mesenchymal traits is seen but tumour cells travel collectively rather than as individuals. In this review, we discuss how crosstalk between a hybrid E/M state and variations in the mechanical aspects of the tumour microenvironment can provide tumour cells with the plasticity required for strategies to navigate surrounding tissues en route to dissemination. Targeting such plasticity provides therapeutic opportunities to combat metastasis.
尽管不同的遗传程序驱动实体瘤的转移,但最终结果是相同的:肿瘤细胞有能力克服一系列物理障碍,从原发肿瘤中逃脱并扩散到其他器官。上皮-间充质转化(EMT)被认为驱动单个细胞从原发肿瘤块中分离,并促进随后在远处器官中建立转移。然而,这一概念受到病理学家观察和动物模型研究的挑战,在这些研究中,观察到部分和短暂获得间充质特征,但肿瘤细胞是集体迁移而不是个体迁移。在这篇综述中,我们讨论了混合 E/M 状态和肿瘤微环境机械方面的变化之间的相互作用如何为肿瘤细胞提供在传播过程中导航周围组织所需的可塑性。针对这种可塑性为治疗转移提供了机会。