Microparticle Phosphatidylserine Mediates Coagulation: Involvement in Tumor Progression and Metastasis

Abstract

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.

Apoptotic cells promote circulating tumor cell survival and metastasis

“…Extracellular vesicles are a source of procoagulant activity and can exhibit pro-metastatic properties (68,72,73). Apoptosis results in membrane blebbing and release of extracellular apoptotic vesicles, but whether there are distinct outcomes depending on whether EVs are derived from live or apoptotic cells is not clear.…”

From Dual Roles to Translational Challenges: Unpacking the Complexities of Tumor-Associated Macrophages in Cancer Progression and Therapy

“…TAMs promote tumor growth and progression through metastasis by secreting pro-tumor factors that can promote several steps of the metastatic cascade, including invasion, internal infiltration, survival in the circulation, extravasation, and colonization of distant organs [15,55,59]. Additionally, TAMs can create a favorable microenvironment for metastatic tumor cells by promoting angiogenesis and inhibiting the immune system, further enhancing the survival and growth of tumor cells in distant areas [1,15,45,60].…”

Potential Associations between Vascular Biology and Hodgkin’s Lymphoma: An Overview

“…This activation may be linked to the increased expression of fibrinolytic proteins, such as tissue plasminogen activator. Such an increase could potentially be associated with vascular remodeling and tumor invasion, thereby contributing to tumor progression [70].…”