Platelets are small anucleate cells present in the blood stream, their typical role in primary hemostasis has been well-described. However, new evidence suggests that they have critically important roles in cancer progression and inflammation. Cancer cells can activate platelets, thus using them as physical shields from blood shear forces and natural killer (NK) cells. The activated platelets may also regulate hematopoietic and immune cell migration toward the tumor site; therefore, contributing to the cancer-associated inflammation. The activation of platelets by cancer cells may also contribute to metastasis and cancer progression by stimulating deep venous thrombosis and neutrophil extracellular trap formations (NETs) that “hide” cancer cells. We strived to review the current literature to dissect the role of platelets in cancer-associated thrombosis and tumor microenvironment inflammation.

The primary hemostatic function of platelets has been recognized for more than a century, but increasing experimental and clinical evidences suggest that platelets are also important mediators of cancer. Cancer indeed influences platelet physiology, and activated platelets participate in each step of cancer development by promoting tumor growth, angiogenesis, metastasis, and cancer-associated thrombosis. Based on both the results of numerous experimental models addressing the involvement of platelets in cancer progression and the results of epidemiologic studies on the use of anti-platelet drugs to prevent cancer, platelets have been proposed as a potential target to reduce the short-term risk of cancer, cancer dissemination and cancer mortality. However, the cancer-associated thrombosis and the risk of bleeding due to anti-platelet drugs are not enough evaluated in experimental models. Therefore, the interesting contribution of platelets to cancer and cancer-associated thrombosis requires the standardization of preclinical and clinical models.

Background The risk of thrombotic complications such as deep vein thrombosis (DVT) during tumor development is well known. Tumors release into circulation procoagulant microparticles (MPs) that can participate in thrombus formation following vessel injury. The importance of this MP tissue factor (TF) in the initiation of cancer-associated DVT remains uncertain. Objective To address how pancreatic cancer MPs promote DVT in vivo. Methods We combined a DVT mouse model where thrombosis is induced by flow restriction of the inferior vena cava with one of subcutaneous pancreatic cancer in C57BL/6J mice. We infused high and low TF tumor MPs to determine the importance of TF in experimental cancer-associated DVT. Results Both tumor-bearing mice and mice infused with tumor MPs submitted to 3 hours of partial flow restriction developed an occlusive thrombus; fewer than a third of the control mice did. We observed that MPs adhered to neutrophil extracellular traps (NETs), functionally important players during DVT, whereas neither P-selectin nor GPIb were required for the MP recruitment in DVT. The thrombotic phenotype induced by MP infusion was suppressed by hirudin suggesting the importance of thrombin generation. TF carried by tumor MPs was essential to promote DVT as mice infused with low TF tumor MPs had less thrombosis than mice infused with high TF tumor MPs. Conclusions TF expressed on tumor MPs contributes to the increased incidence of cancer-associated venous thrombosis in mice in vivo. These MPs may adhere to NETs formed at the site of thrombosis.