Abstract
Although platelets are critically involved in thrombosis and hemostasis, experimental and clinical evidence indicate that platelets promote tumor progression and metastasis through a wide range of physical and functional interactions between platelets and cancer cells. Thrombotic and thromboembolic events are frequent complications in patients with solid tumors. Hence, cancer modulates platelet function by directly inducing platelet-tumor aggregates and triggering platelet granule release and altering platelet turnover. Also, platelets enhance tumor cell dissemination by activating endothelial cell function and recruiting immune cells to primary and metastatic tumor sites. In this review, we summarize current knowledge on the complex interactions between platelets and tumor cells and the host microenvironment. We also critically discuss the potential of anti-platelet agents for cancer prevention and treatment.
Highlights
Cancer is caused by uncontrolled cell division and growth of malignant cells, which can spread throughout the body, resulting in metastasis [1, 2]
Using different in vivo experimental settings, inhibition of tissue factor (TF), depletion of neutrophils, or administration of deoxyribonuclease I (DNAse I) in mice could inhibit venous thrombosis [45]. These results suggest that systemic DNAse I treatment degrading Neutrophil extracellular trap (NET) can inhibit cancer-associated thrombosis and tumor growth
nectin-like molecule 5 (NECL5) interacts with CD226 on the platelet surface, enabling tumor cell adhesion to the endothelial vasculature, thereby leading to tumor metastasis [132]. aVb3 integrin on breast cancer cells can bind to platelet-derived autotaxin which is stored in a-granules and secreted into the vasculature upon platelet activation [133, 134]
Summary
Cancer is caused by uncontrolled cell division and growth of malignant cells, which can spread throughout the body, resulting in metastasis [1, 2]. Thrombotic events have been frequently observed in cancer patients indicating an active involvement of platelets and factors released from platelets in tumor progression, enhancing procoagulant activity and blood clotting [12, 13]. In mouse models of colorectal and ovarian carcinoma, the inflammatory response of tumor and immune cells involves IL-6 production that can stimulate platelet production by enhancing TPO secretion from hepatocytes [19, 22] This pathological process is inhibited in IL-6-deficient mice, confirming the paraneoplastic effect of IL-6 in colorectal carcinoma-induced thrombocytosis [22]. Inhibition of platelet CLEC-2 function in a mouse model of lung cancer significantly reduces thrombus formation and metastatic events after injection of B16F10 melanoma cells, suggesting that interaction between platelet CLEC-2 and cancerresident PDPN may enhance thromboembolism, TCIPA and platelet-dependent tumor cell spreading in human patients [33]. These results suggest that platelets and their granular content may contribute to the formation of ETs, supporting thrombus formation and coagulopathy in cancer patients
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