Microparticle Phosphatidylserine Mediates Coagulation: Involvement in Tumor Progression and Metastasis

Simple Summary: Microparticles (MPs) play a key role in intercellular communication and mediate many features of cancers by delivering their various biomolecular cargos (including phospholipids). Increased release of phosphatidylserine-rich MPs from cancer and blood cells promotes tumor development and progression. Cancer cell signaling contributes to the formation of hypercoagulability, which in turn facilitates tumor progression. This review links coagulation activation with the process of metastatic tumor spread, including angiogenesis and matrix degradation. Therefore, anticoagulation can not only reduce thrombus formation but also slow tumor progression, which is of great significance for patient treatment. We provide promising cancer treatment strategies targeting the phosphatidylserine-mediated coagulation cascade and fill current knowledge gaps.Tumor progression and cancer metastasis has been linked to the release of microparticles (MPs), which are shed upon cell activation or apoptosis and display parental cell antigens, phospholipids such as phosphatidylserine (PS), and nucleic acids on their external surfaces. In this review, we highlight the biogenesis of MPs as well as the pathophysiological processes of PS externalization and its involvement in coagulation activation. We review the available evidence, suggesting that coagulation factors (mainly tissue factor, thrombin, and fibrin) assist in multiple steps of tumor dissemination, including epithelial-mesenchymal transition, extracellular matrix remodeling, immune escape, and tumor angiogenesis to support the formation of the pre-metastatic niche. Platelets are not just bystander cells in circulation but are functional players in primary tumor growth and metastasis. Tumor-induced platelet aggregation protects circulating tumor cells (CTCs) from the blood flow shear forces and immune cell attack while also promoting the binding of CTCs to endothelial cells and extravasation, which activates tumor invasion and sustains metastasis. Finally, in terms of therapy, lactadherin can inhibit coagulation by competing effectively with coagulation factors for PS binding sites and may similarly delay tumor progression. Furthermore, we also investigate the therapeutic potential of coagulation factor inhibitors within the context of cancer treatment. The development of multiple therapies targeting platelet activation and platelet-tumor cell interactions may not only reduce the lethal consequences of thrombosis but also impede tumor growth and spread.