Institut Curie, PSL Research University, CNRS, UMR 144, Paris, France.
Translational Medical Oncology; Health Research Institute of Santiago (IDIS); SERGAS, Santiago de Compostela, Spain.
Cancer Res. 2017 Jul 1;77(13):3431-3441. doi: 10.1158/0008-5472.CAN-16-1917. Epub 2017 May 23.
The interaction between circulating tumor cells (CTC) and endothelial cells during extravasation is a critical process during metastatic colonization, but its mechanisms remain poorly characterized. Here we report that the luminal side of liver blood vessels contains fibronectin deposits that are enriched in mice bearing primary tumors and are also present in vessels from human livers affected with metastases. Cancer cells attached to endothelial fibronectin deposits via talin1, a major component of focal adhesions. Talin1 depletion impaired cancer cell adhesion to the endothelium and transendothelial migration, resulting in reduced liver metastasis formation Talin1 expression levels in patient CTC's correlated with prognosis and therapy response. Together, our findings uncover a new mechanism for liver metastasis formation involving an active contribution of hepatic vascular fibronectin and talin1 in cancer cells. .
循环肿瘤细胞（CTC）与血管内皮细胞在血管外渗过程中的相互作用是转移定植过程中的一个关键步骤，但其中的机制仍知之甚少。在这里，我们报告说，肝脏血管的管腔侧含有富含纤维连接蛋白的沉积物，这些沉积物在携带原发性肿瘤的小鼠中丰富存在，并且在来自患有转移的人类肝脏的血管中也存在。癌细胞通过粘着斑的主要成分塔林 1 附着在内皮纤维连接蛋白沉积物上。塔林 1 的耗竭会损害癌细胞与内皮细胞的黏附以及细胞穿过内皮细胞的迁移能力，从而导致肝脏转移形成减少。患者 CTC 中的塔林 1 表达水平与预后和治疗反应相关。总之，我们的研究结果揭示了一种涉及肝血管纤维连接蛋白和癌细胞中塔林 1 的积极作用的新的肝脏转移形成机制。
