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Contribution of platelets to tumour metastasis

Abstract

Extensive experimental evidence shows that platelets support tumour metastasis. The activation of platelets and the coagulation system have a crucial role in the progression of cancer. Within the circulatory system, platelets guard tumour cells from immune elimination and promote their arrest at the endothelium, supporting the establishment of secondary lesions. These contributions of platelets to tumour cell survival and spread suggest platelets as a new avenue for therapy.

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Figure 1: Platelet biology.
Figure 2: Molecular coordination between platelets and tumour cells supports metastasis from the bloodstream.

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Acknowledgements

B.F.H. is supported by grants from the US National Institutes of Health (NIH) (CA 112287), the California Breast Cancer Research Program (12NB0176 and 13NB0180) and the US Department of Defense (W81XWH-08-1-0468). L.J.G. is supported by a trainee scholarship from NIH grant 5TL1RR025772-03.

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Glossary

Blood perfusion model

Parallel plate flow chamber system in which adhesive interactions between blood-borne tumour cells, blood cells, platelets and endothelial cells are monitored and measured by video microscopy.

Disseminated intravascular coagulation

Pathological activation of coagulation (blood clotting) mechanisms that leads to the formation of small blood clots in blood vessels throughout the body.

Endothelial retraction

Disruption of adherens junctions of endothelial cells creates gaps in the endothelial monolayer and increases vascular permeability while exposing the matrix proteins of the basement membrane.

Glycoconjugates

Carbohydrate-linked lipids and proteins, which include receptors and ligands that function as cell adhesion molecules.

Migratory thrombophlebitis

Malignancy-associated hypercoagulable state leading to spontaneous platelet-rich clots in veins anywhere in the body that dynamically form, resolve and reappear.

Paraneoplastic disease

Disease induced as a result of tumour burden; generally caused by the release of tumour-derived hormones, peptides or cytokines, or by the misguided destruction of normal tissue by immune cells targeted against malignant cells.

Pulmonary embolism

Blockage of the main artery of the lung or one of its branches by a platelet-rich clot that originated in the venous circulation and dislodged from where it initially formed.

Shear stress

The velocity of flowing blood is highest in the centre of vessels and decreases towards the vessel wall, resulting in differential flow that generates a shearing force.

Thromboembolic disease

Condition caused by travelling blood clots or emboli that occlude blood vessels; commonly manifesting as deep vein thrombosis or pulmonary embolism in cancer patients.

Weibel–Palade bodies

Secretory granules of endothelial cells that particularly store and secrete multimerized von Willebrand factor, and which translocate P-selectin to the membrane surface on cell activation.

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Gay, L., Felding-Habermann, B. Contribution of platelets to tumour metastasis. Nat Rev Cancer 11, 123–134 (2011). https://doi.org/10.1038/nrc3004

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