Janus-Bell Emily, Liboni Cristina, Yakusheva Alexandra, Mittelheisser Vincent, Mouriaux Clarisse, Bourdon Catherine, Bochler Louis, Hyenne Vincent, Garcia-Leon Maria, Lefebvre Olivier, Goetz Jacky G, Mangin Pierre H
Université de Strasbourg, INSERM, EFS Grand Est, BPPS UMR-S1255, FMTS, 67065 Strasbourg, France.
Tumor Biomechanics, INSERM UMR_S1109, 67000 Strasbourg, France.
iScience. 2025 Jul 31;28(9):113250. doi: 10.1016/j.isci.2025.113250. eCollection 2025 Sep 19.
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.
血小板整合素与其他血小板受体一起，已知可控制止血和血栓形成，还能影响肿瘤转移进程。然而，它们单独或联合缺乏对这些过程的影响从未得到过测试。在PF4Cre-β1/β3小鼠品系中，我们发现血小板完全缺乏所有整合素。虽然它们与纤维蛋白原和膜联蛋白V的结合受损，但P-选择素的暴露正常。在剪切流作用下，血小板在固定化纤维蛋白原和纤维状纤连蛋白上的黏附被消除。PF4Cre-β1/β3小鼠的出血时间延长，在动脉血栓形成的实验模型中存在严重缺陷。血小板对肿瘤细胞的黏附也减少，对三阴性乳腺癌模型中的肿瘤生长和转移负担有显著影响。总体而言，这些结果证实了血小板整合素在止血和血栓形成中的核心作用，并突出了它们对肿瘤生长和转移形成的贡献。
