Tumor–platelet interaction in solid tumors

Abstract

Elevated platelet counts in patients diagnosed with malignant tumors were first described more than 100 years ago. Today it is well known that in many types of solid tumors, thrombocytosis at the time of diagnosis is associated with shorter survival. From this well-documented clinical correlation between platelet count and prognosis of solid tumors, the following questions arise: (i) Are the increased platelet counts the reason for shortened survival as platelet-secreted cytokines might boost tumor growth and angiogenesis? (ii) Do platelets affect tumor metastasis thereby shortening survival time? or (iii) Are increased platelet counts simply an epiphenomenon of tumor growth with larger tumors resulting in higher platelet counts and shorter survival times? We address these three questions within our review of the current literature to provide a comprehensive overview of the current concepts in tumor-platelet interaction.

Risk of posttransplant hepatocellular carcinoma recurrence is greater in recipients with higher platelet counts in living donor liver transplantation

“…(31) In contrast, solid tumors enhance hepatic thrombopoietin synthesis by releasing thrombopoietic cytokines, whereas more aggressive tumors induce a greater degree of thrombocytosis. (7,32) Accordingly, parenchymal liver disease status and tumor biology were significantly different between the 2 groups in this study. Because some determinants of PLT are also contributors to posttransplant outcomes, the success of the study mainly depends on determining whether or not the PLT is an epiphenomenon.…”

“…(11) During the metastatic cascade, platelets interact with tumor cells at every step in circulation as well as at the site of distant metastases while directly enhancing invasive potential or indirectly modulating the microenvironment. (6,7,24,25) For example, platelet-tumor cell crosslinking forms a shield around tumor cells and protects them from mechanical destruction by hemodynamic shear forces and immunologic lysis by natural killer cells. It also promotes arrest of tumor cells to the secondary site through rolling and tethering to the vessel wall.…”

“…(6,26) Whereas extensive experimental research has outlined the platelet-cancer loop, clinical studies also support the importance of platelets by demonstrating an association between PLT and poor prognosis in cancers of various organs including the liver. (7,9,27) Of interest, sorafenib, which is the first systemic drug to be approved for the management of advanced HCC, suppresses HCC progress by inhibiting cellular signaling mediated by platelet-derived growth factors such as vascular endothelial growth factor and platelet-derived growth factor. (28) The current and previous studies have consistently demonstrated that early posttransplant PLT is mainly determined by preoperative PLT.…”

“…Preoperative PLT was negatively associated with the amount of transfused platelets during surgery (coefficient -0.49; P < 0.001), during the first week after surgery (coefficient -0.55; P < 0.001), and between 1 and 2 weeks after surgery (coefficient -0.21; P < 0.001). Accordingly, the amount of transfused platelets during surgery, during the first week after surgery, and between 1 and 2 weeks after surgery was 0 (0-6), 9 (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22), and 0 (0-0) units in the low platelet group and 0 (0-0), 0 (0-4), and 0 (0-0) units in the high platelet group, respectively, where 1 unit of apheresis platelets was considered to be equivalent to 6 units of platelets, as described previously. (22) Minimum PLT measured at each postoperative day during the first 2 weeks after transplantation was consistently <30 3 10 9 /L in median within the subgroup of recipients who underwent platelet transfusion on each corresponding day, indicating that platelet transfusion was performed according to our standardized protocol targeting PLT >30 3 10 9 /L (Supporting Fig.…”

“…(9) The relationship between platelets and tumors is not a simple epiphenomenon resulting from tumor-induced thrombopoiesis, but rather a direct contribution of platelets to multiple steps in the cancer progression, including tumor cell angiogenesis, protection from immune attack, extravasation, and arrest within the vasculature. (6,7,10,11) A previous study in hepatitis B virus (HBV) transgenic mice clearly demonstrated that antiplatelet treatment reduced intrahepatic inflammatory response and HCC development with improved longterm survival. (12) Thus, we hypothesized that the risk of HCC recurrence after living donor liver transplantation is affected by platelets.…”