title: Effects of cancer on platelets.
abstract: The main function of circulating platelets is to stop bleeding upon vascular injury by the formation of a hemostatic plug. The presence of cancer results in numerical and functional abnormalities of platelets. Thrombocytosis is commonly observed in cancer patients and is associated with decreased survival. Conversely, thrombocytopenia has been shown to have antimetastatic effects in experimental models. Tumor cells also can induce changes in the platelet activation status, both in direct and indirect manners. Direct tumor cell-induced platelet aggregation enables the formation of a cloak of aggregated platelets around circulating tumor cells (CTCs) that shields them from attacks by the immune system and facilitates metastasis to distant sites. Cancer also can induce platelet activation in various indirect ways. Tumor cells shed small extracellular vesicles that expose the transmembrane protein tissue factor (TF)--the initiator of the extrinsic coagulation cascade. The abundant presence of TF in the circulation of cancer patients can result in local generation of thrombin, the most potent platelet activator. Another pathway of indirect platelet activation is by increased formation of neutrophil extracellular traps in the presence of tumor-secreted granulocyte colony-stimulating factor (G-CSF). Last, tumor cells may regulate the selective secretion of angiogenic proteins from platelet granules, which enables the tumor to stimulate and stabilize the immature neovasculature in the tumor environment. Since there is little doubt that the cancer-induced platelet alterations are beneficial to tumor growth and dissemination, it could be worthwhile to intervene in the underlying mechanisms for anticancer purposes. Antiplatelet and anticoagulant agents that inhibit platelet activation and thrombin generation can potentially slow cancer progression, although the clinical evidence thus far is not unequivocal.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands. Electronic address: n.vanes@amc.nl.
authors.forename: Nick
authors.initials: N
authors.lastname: van Es
authors.affiliation: Department of Clinical Chemistry, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Auguste
authors.initials: A
authors.lastname: Sturk
authors.affiliation: Department of Vascular Medicine, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Saskia
authors.initials: S
authors.lastname: Middeldorp
authors.affiliation: Department of Clinical Chemistry, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Rienk
authors.initials: R
authors.lastname: Nieuwland
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000473:pathology*; D006801:Humans; D009369:Neoplasms / Q000150:complications / Q000503:physiopathology*; D013921:Thrombocytopenia / Q000209:etiology*