Platelet-Derived Factor V Is an Important Determinant of the Metastatic Potential of Circulating Tumor Cells.

Xin Deng,Rong Li,Yongjie Li,Mao Luo,Yifei Deng,Jianbo Wu,Liqun Wang,Ni Chen,Luochen Zhu,Ziqian Feng

doi:10.3389/fonc.2020.558306

Abstract

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. In vitro, 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.

Highlights

The association between coagulation activation and tumor progression is well documented [1,2,3]
We compared the number of lung metastasis between Tg−F5+/+, Tg+F5+/−, and Tg+F5−/− mice to determine the effect of platelet-derived Factor V (FV) on metastasis
We further investigated the effect of an FV antibody in vivo using an experimental metastasis model with C57BL/6J mice

Summary

INTRODUCTION

The association between coagulation activation and tumor progression is well documented [1,2,3]. A crucial step in cancer metastasis is the survival of cancer cells in the circulation This process involves the interactions of tumor cells with platelets, shielding them from immune responses in the circulation [4,5,6]. As shown in our recent study, platelet-derived FV plays an important role in controlling angiogenesis and is likely associated with thrombin activity [16]. Using transgenic mice that express different levels of the FV gene in either plasma or platelets [17], we recently identified a critical role for platelet-derived FV in the regulation of arterial thrombosis through platelet activation [18]. We evaluated the role of FV from different sources in metastasis

MATERIALS AND METHODS

RESULTS AND DISCUSSION

ETHICS STATEMENT