Role of Platelet Activation in the Development and Metastasis of Solid Tumors

The blood coagulation system is actively involved in the developmentof cancer. Many solid tumors express tissue factor (TF) that triggersa plasma coagulation cascade leading to an increased risk of cancer-associatedthrombosis and venous thrombosis in cancer patients. The main componentsof the blood clots, platelets are also well known for their rolein cancer metastasis as they bind to tumor cells once they enterblood vessels and “shield” them to escape immune surveillance. Plateletsalso promote adhesion and extravasation of circulating tumor cellsinto tissues and subsequent metastasis formation. Moreover, beingmobile carriers of various growth factors, platelets are activelyrecruited and, in some cases, engulfed by the tumor, contributingthereby to tumor development and vascularization. Platelet recruitmentoccurs through both tumor-induced thrombin activation and exposingof platelet-adhesive surfaces by the tumor. Activated in the tumorproximity, platelets attract and induce neutrophil activation andthe formation of neutrophil extracellular traps (NETs), thus modulatingthe tumor microenvironment. Apart from direct interaction, plateletsand tumor cells exchange mRNA, miRNA and other regulatory moleculesvia microvesicles, with platelets serving as “containers” that spread tumorgenetic material (circulating nucleic acids) throughout the organism.In this review, we address the molecular mechanisms behind the plateletinvolvement in the growth and metastasis of solid tumors, and discusspossible options for the pharmacological interruption of platelet–tumorcell interaction.