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.