Abstract
Spontaneous venous thrombosis is often the first clinical sign of cancer, and it is linked to a worsened survival rate. Traditionally, tumor-cell induced platelet activation has been the main actor studied in cancer-associated-thrombosis. However, platelet involvement alone does not seem to be sufficient to explain this heightened pro-thrombotic state. Neutrophils are emerging as key players in both thrombus generation and cancer progression. Neutrophils can impact thrombosis through the release of pro-inflammatory cytokines and expression of molecules like P-selectin and Tissue Factor (TF) on their membrane and on neutrophil-derived microvesicles. Their role in cancer progression is evidenced by the fact that patients with high blood-neutrophil counts have a worsened prognosis. Tumors can attract neutrophils to the cancer site via pro-inflammatory cytokine secretions and induce a switch to pro-tumoral (or N2) neutrophils, which support metastatic spread and have an immunosuppressive role. They can also expel their nuclear contents to entrap pathogens forming Neutrophil Extracellular Traps (NETs) and can also capture coagulation factors, enhancing the thrombus formation. These NETs are also known to have pro-tumoral effects by supporting the metastatic process. Here, we strived to do a comprehensive literature review of the role of neutrophils as drivers of both cancer-associated thrombosis (CAT) and cancer progression.
Highlights
The connection between cancer and thrombosis has been described since the XIX century by Dr Trousseau who described the presence of spontaneous coagulation in oncological patients [1,2]
Human Neutrophil-MVs obtained after a PMA stimulation contain functionally active MAC-1 integrins that interact with GPIb on resting platelets
We have endeavored to describe the current state of the literature on the relationship between neutrophils, thrombosis, and cancer
Summary
The connection between cancer and thrombosis has been described since the XIX century by Dr Trousseau who described the presence of spontaneous coagulation in oncological patients [1,2]. Tumor-activated platelets can secrete growth factors into the tumor microenvironment like transforming growth factor beta (TGF-β), vascular endothelial growth factor (VEGF), and platelet derived growth factor (PDGF) [2,13,16] This platelet degranulation can support local angiogenesis and increase the endothelial expression of adhesion molecules [13,17,18]. This overall increased platelet activity is related to a heightened risk of venous and arterial thrombosis in cancer patients [2,19,20,21]. In this review will strive to compile the current state of the art of neutrophil involvement in cancer progression and in cancer-associated thrombosis
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