Depletion of all platelet integrins impacts hemostasis, thrombosis, and tumor metastasis

Platelet integrins, together with other platelet receptors, are known to control hemostasis and thrombosis but also metastatic progression. However, the impact of their exclusive but combined deficiency has never been tested in these processes. In a PF4Cre-β1(-/-)/β3(-/-) mouse strain, we found that platelets were exclusively depleted of all integrins. While they displayed impaired binding to fibrinogen and annexin V, P-selectin exposure was normal. Platelet adhesion was abrogated on immobilized fibrinogen and fibrillar fibronectin under shear flow. PF4Cre-β1(-/-)/β3(-/-) mice presented an increased bleeding time and a profound defect in experimental models of arterial thrombosis. Platelet adhesion to tumor cells was also reduced, with a pronounced effect on tumor growth and metastatic burden in a model of triple negative breast cancer. Overall, these results confirm the central role of platelet integrins in hemostasis and thrombosis, and highlight their contribution to tumor growth and metastasis formation.