The regulation of cancer-associated thrombosis by podoplanin.

The incidence of venous thromboembolism (VTE) in cancer patients is 4-9 fold higher compared with the general population. The mortality rate of patients with cancer and VTE is more than 2-fold greater versus cancer patients without VTE. Given that the pathophysiology of thrombosis in cancer is multi-faceted, investigations of the mechanisms that regulate cancer-associated thrombosis (CAT) could improve the understanding and treatment of CAT. These mechanisms include activation of the coagulation and fibrinolytic systems. Tumor cells activate coagulation by expressing procoagulant molecules, releasing pro-inflammatory and pro-angiogenic cytokines, and adhering to vascular and blood cells. Tumor-secreted and tissue factor-positive extracellular vesicles are another major driver of CAT, while emerging studies have discovered a role for podoplanin (PDPN) in intratumoral thrombosis, hyper-coagulation, and enhanced VTE risk. In this article, we will review studies of PDPN in CAT, which together suggest that PDPN contributes not only to cancer progression and metastasis, but also to CAT. PDPN may therefore represent an attractive putative target for therapies that aim to simultaneously reduce cancer progression and associated VTE.