首页> 外文OA文献 >Thrombin promotes platelet-mediated melanoma cell adhesion to endothelial cells under flow conditions: role of platelet glycoproteins P-selectin and GPIIb-IIIA.
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Thrombin promotes platelet-mediated melanoma cell adhesion to endothelial cells under flow conditions: role of platelet glycoproteins P-selectin and GPIIb-IIIA.

机译:凝血酶在流动条件下促进血小板介导的黑色素瘤细胞粘附于内皮细胞:血小板糖蛋白P-选择蛋白和GPIIb-IIIA的作用。

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摘要

We investigated the role of platelets in human melanoma cell (line 397) interaction with vascular endothelial cells (ECs) under flow conditions. The ability of the tumour cells to adhere to the EC monolayer was significantly reduced by application of flow at a shear rate of 250 s(-1). A 2.2-fold increase in tumour cell adhesion to ECs under flow was observed upon addition of thrombin receptor agonist peptide (TRAP)-activated platelets but not resting platelets. A similar increase (2.5-fold) in tumour cell adhesion to ECs under flow was observed when the tumour cells were incubated with resting platelets on thrombin-treated ECs. However, thrombin treatment of the ECs alone had no effect on tumour cell adhesion in the absence of platelets. The enhancement of tumour cell adhesion to ECs by TRAP-activated platelets was virtually abolished by blockade of the platelet glycoproteins P-selectin and GPIIb-IIIa by monoclonal antibodies. Blockade of P-selectin also inhibited the direct adhesion of TRAP-activated platelets to ECs, but did not affect the interaction of the tumour cells with platelets immobilized on subendothelial extracellular matrix (ECM). Blockade of GPIIb-IIIa inhibited both platelet-EC and platelet-tumor cell interactions. Our results indicate that tumour cell adhesion to the endothelium under flow is enhanced by platelets under conditions that allow platelet adhesion to ECs. Inhibition studies suggest that activated platelet adhesion to ECs is mediated by P-selectin and GPIIb-IIIA, and tumour cell adhesion to EC-bound platelets--mainly by GPIIb-IIIa.
机译:我们研究了血小板在血流条件下与血管内皮细胞(EC)相互作用的人类黑素瘤细胞(397行)中的作用。通过以250 s(-1)的剪切速率施加流量,肿瘤细胞粘附到EC单层的能力大大降低。加入凝血酶受体激动剂肽(TRAP)激活的血小板但未静息血小板后,发现在流动状态下肿瘤细胞对EC的粘附力增加了2.2倍。当将肿瘤细胞与凝血酶处理的ECs上的静息血小板一起孵育时,观察到肿瘤细胞在流动状态下与ECs的粘附性类似增加(2.5倍)。然而,在没有血小板的情况下,仅对凝血酶的凝血酶治疗对肿瘤细胞粘附没有影响。通过单克隆抗体阻断血小板糖蛋白P-选择蛋白和GPIIb-IIIa,实际上消除了TRAP活化的血小板增强的肿瘤细胞对ECs的粘附。对P-选择蛋白的阻断也抑制了TRAP活化的血小板与EC的直接粘附,但不影响肿瘤细胞与固定在内皮下细胞外基质(ECM)上的血小板的相互作用。 GPIIb-IIIa的阻滞抑制了血小板EC和血小板肿瘤细胞的相互作用。我们的结果表明,在允许血小板粘附至EC的条件下,血小板可增强肿瘤细胞对血管内皮细胞的粘附。抑制研究表明,活化的血小板对EC的粘附是由P-选择素和GPIIb-IIIA介导的,而肿瘤细胞对EC结合的血小板的粘附-主要是由GPIIb-IIIa介导的。

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