Platelet Contribution to the Formation of Metastatic Foci: The Role of Cancer Cell-Induced Platelet Activation

Abstract

Platelets are thought to be involved in the development of blood borne metastasis. Ultrastructural and experimental studies demonstrate that association between tumor cells and platelets with subsequent activation of the coagulation cascade takes place in malignancy. Several hypotheses have been proposed to explain the mechanisms by which tumor cells activate platelets including generation of thrombin, ADP release and involvement of arachidonate metabolism. Perfusion studies with human homologous systems showed that intact tumor cells and tumor cell microvesicles were able to induce platelet thrombogenicity under defined flow conditions. The presence of divalent cations and plasma factors was necessary for the cancer cells to exert their activating capacity. These results suggest a role for platelets in the development of secondary metastasis as well as in the thrombotic events of malignancy.

Increased thromboembolic incidence in anti-cardiolipin-positive patients with malignancy

“…A number of mechanisms have been proposed to explain the association of malignancy and thrombosis: activation of clotting factors (Gordon et al, 1975;Naschitz et al, 1993), tumour interaction with vascular endothelium (Warren and Vales, 1972;Al-Mondhiry and McGarvey, 1987) and platelet activation by cancer cells (Bastida and Ordinas, 1988;Naschitz et al, 1993). The increased presence of antiphospholipid/anti-cardiolipin antibodies in patients with cancer may be a contributory factor in the paraneoplastic development of vascular thrombosis in these patients.…”

Platelet-derived thrombospondin-1 is a critical negative regulator and potential biomarker of angiogenesis

“…5,6 By adhering to the endothelium of injured tissues and then secreting their granular contents, platelets deposit high concentrations of angiogenesisregulatory proteins in a regulated and localized manner. Tumor cells are also known to promote platelet activation and aggregation by the release of platelet-activating factors, such as thrombin and adenosine diphosphate, 13 resulting in the release of ␣ granules and their content, which in turn directly affects tumor growth. 14 Recently, we have described the storage of proangiogenic and antiangiogenic factors within separate platelet ␣ granules, 5 whereas others have demonstrated selective release of either proangiogenic or antiangiogenic proteins on platelet activation.…”

P-selectin mediates adhesion of platelets to neuroblastoma and small cell lung cancer.

“…Several lines of investigation suggested that platelets facilitate blood-born metastasis (1)(2)(3)(4). Gasic and colleagues (5) first noted that the number of experimentally induced pulmonary metastasis was reduced in mice when they were made thrombocytopenic before the injection of tumor cells and that the incidence of metastasis was positively correlated to the platelet count.…”