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

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

JOURNAL=Frontiers in Oncology

VOLUME=Volume 10 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.558306

DOI=10.3389/fonc.2020.558306

ISSN=2234-943X

ABSTRACT=Factor V (FV) is a critical component in the blood coagulation cascade. In patients, FV inhibitors ihave been reported in association with malignancy. FV is found in plasma and platelet, which exhibited physical and functional differences. However, the functions of FV in cancer progression remains poorly understood. Whether FV is a determinant of the metastatic potential of circulating tumor cells, we evaluated the impact of different levels of FV in plasma and platelets on the hematogenous mouse pulmonary metastasis model. 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. 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 increased adhesion to endothelial cells that treated with lower levels of platelet FV, but not platelet-poor plasma. Furthermore, platelets from mice with lower platelet FV expressed lower levels of TFPIα compared with mice with higher platelet FV. These findings suggest that platelet-derived FV contributes to the hematogenous pulmonary metastasis, and is associated with the regulation of tumor cell adhesion to vessel wall.