Deng Xin, Feng Ziqian, Zhu Luochen, Chen Ni, Deng Yifei, Li Yongjie, Li Rong, Wang Liqun, Luo Mao, Wu Jianbo
Key Laboratory of Medical Electrophysiology of Ministry of Education, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province, Drug Discovery Research Center, Southwest Medical University, Luzhou, China.
Laboratory for Cardiovascular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China.
Front Oncol. 2020 Sep 23;10:558306. doi: 10.3389/fonc.2020.558306. eCollection 2020.
Factor V (FV) is a critical component in the blood coagulation cascade. In patients, FV inhibitors have been reported to be associated with malignancy. FV is present in plasma and platelets, which exhibit physical and functional differences. However, the functions of FV in cancer progression remain poorly understood. We evaluated the impact of different levels of FV in plasma and platelets on the haematogenous mouse pulmonary metastasis model to determine whether FV determines the metastatic potential of circulating tumor cells. The role of platelet-derived FV was evaluated using a murine B16F10 pulmonary metastasis model, an assay of tumor cell adhesion to endothelial cells, and western blotting. By combining genetic models and FV inhibitory antibody, the transgenic mice with lower platelet FV expression showed significant increases in metastases compared with mice with higher platelet FV expression. , labeled B16F10 melanoma cells appeared to exhibit increased adhesion to endothelial cells that were treated with lower levels of platelet FV, but not platelet-poor plasma. Furthermore, platelets from mice with lower platelet FV levels expressed TFPIα at lower levels than with mice with higher platelet FV expression. Based on these findings, platelet-derived FV contributes to haematogenous pulmonary metastasis and is associated with the regulation of tumor cell adhesion to the vessel wall.
凝血因子V（FV）是血液凝固级联反应中的关键成分。在患者中，据报道FV抑制剂与恶性肿瘤有关。FV存在于血浆和血小板中，它们在物理和功能上存在差异。然而，FV在癌症进展中的作用仍知之甚少。我们评估了血浆和血小板中不同水平的FV对血行性小鼠肺转移模型的影响，以确定FV是否决定循环肿瘤细胞的转移潜能。使用小鼠B16F10肺转移模型、肿瘤细胞与内皮细胞粘附试验以及蛋白质印迹法评估血小板衍生FV的作用。通过结合遗传模型和FV抑制抗体，与血小板FV表达较高的小鼠相比，血小板FV表达较低的转基因小鼠转移明显增加。标记的B16F10黑色素瘤细胞似乎对用较低水平血小板FV处理的内皮细胞表现出增加的粘附，但对缺乏血小板的血浆处理的内皮细胞没有增加的粘附。此外，血小板FV水平较低的小鼠的血小板表达组织因子途径抑制物α（TFPIα）的水平低于血小板FV表达较高的小鼠。基于这些发现，血小板衍生的FV促进血行性肺转移，并与肿瘤细胞对血管壁的粘附调节有关。
