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

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.

Haemodynamic-dependent arrest of circulating tumour cells at large blood vessel bifurcations as new model for metastasis

“…Interestingly, variations in the haematocrit can modulate the adhesion of CTC to the vessel wall, their velocity in the blood flow and red blood cell aggregation 28 . Similarly, factors of the coagulation cascade, as factor V, have demonstrated a role in the interaction of the CTC with the vascular endothelium and the efficiency of metastasis 29 . From a therapeutic perspective, anticoagulant drugs as low molecular weight heparin and warfarin, contributing to reduce blood viscosity, have shown antitumor and antimetastatic activity 30,31 .…”

Minimal Residual Disease, Metastasis and Immunity

“…Individual CTC detachment from the ECM may also induce anoikis that can be overcome by tight junction maintenance in circulating clusters [36]. Several recent studies have shown that hyper-activated platelets adhere to CTC clusters and secrete soluble effectors conferring enhanced survival properties and increased metastatic efficiency to CTCs [37][38][39][40]. In this context, Yu and colleagues described that platelet-tumor cell interaction through Toll-like receptor 4 (TLR4) promotes tumor metastasis [41].…”