Heterogeneous Responses to Mechanical Force of Prostate Cancer Cells Inducing Different Metastasis Patterns
Heterogeneous Responses to Mechanical Force of Prostate Cancer Cells Inducing Different Metastasis Patterns
复制标题
前列腺癌细胞对机械力的异质反应诱导不同的转移模式
DOI：
10.1002/advs.201903583
复制
发表时间：
2020-06-17
期刊：
影响因子：
15.1
通讯作者：
Wang，Yue
中科院分区：
文献类型：
--
作者：
Liu，Zhixiao;Wang，Liujun;Wang，Yue
细胞外环境的物理信号在癌细胞转移过程中起着重要作用。然而，转移性癌细胞如何对转移部位的不同机械环境作出反应尚不完全清楚。在这里，制备了具有不同力学性能的基质来模拟各种人体组织的细胞外力学环境。来自不同转移部位的前列腺癌（PC）细胞在机械反应上表现出异质性。这种异质性介导了两种不同的转移模式。高刚度通过诱导骨转移源细胞中的Yes相关蛋白和他法津（YAP/TAZ）核定位来促进单个细胞的迁移和增殖，而低刚度通过诱导淋巴转移源细胞形成以CD44高表达为特征的簇来促进细胞的迁移和增殖。细胞外环境的力学特性诱导的不同转移模式在PC的发展中起着至关重要的作用。
The physical cues in the extracellular environment play important roles in cancer cell metastasis. However, how metastatic cancer cells respond to the diverse mechanical environments of metastatic sites is not fully understood. Here, substrates with different mechanical properties are prepared to simulate the extracellular mechanical environment of various human tissues. The prostate cancer (PC) cells derived from different cancer metastasis sites show heterogeneity in mechanical response. This heterogeneity mediates two distinct metastasis patterns. High stiffness promotes individual cell migration and proliferation by inducing Yes‐associated protein and tafazzin (YAP/TAZ) nuclear localization in bone metastasis‐derived cells, whereas low stiffness promotes cell migration and proliferation by inducing lymphatic metastasis‐derived cells to form clusters characterized by high expression of CD44. The different metastasis patterns induced by the mechanical properties of the extracellular environment are crucial in the development of PC.