Faulkner Lucy G, Alqarni Saeed, Maraveyas Anthony, Madden Leigh A
Queens Centre for Oncology and Haematology, Castle Hill Hospital, Cottingham.
Department of Biomedical Science, University of Hull, Hull, UK.
Blood Coagul Fibrinolysis. 2020 Jan;31(1):35-42. doi: 10.1097/MBC.0000000000000876.
: Cancer induces a hypercoagulable state, resulting in an increased risk of venous thromboembolism. One of the mechanisms driving this is tissue factor (TF) production by the tumour, released in small lipid bound microparticles. We have previously demonstrated that tumour cell line media-induced procoagulant changes in HUVEC. The aim of this study was to investigate the effect of tumour microparticles and recombinant human TF (rhTF) on the endothelium. Procoagulant microparticles from the PANC-1 cell line were harvested by ultrafiltration. HUVEC were then incubated with these procoagulant microparticles or rhTF. Flow cytometry was used to investigate the effect of endothelial cell surface protein expression and microparticle release. Microparticles but not soluble TF was responsible for the procoagulant activity of cell-free tumour media. We also demonstrated an increase in endothelial microparticle release with exposure to tumour microparticles, with a positive linear relationship observed (R = 0.6630 P ≤ 0.0001). rhTF did not induce any of the changes observed with microparticles. Here we demonstrate that procoagulant activity of tumour cell line media is dependent on microparticles, and that exposure of endothelial cells to these microparticles results in an increase in microparticle release from HUVEC. This suggests a mechanism of transfer of procoagulant potential from the cancer to the remote endothelium.
癌症会引发高凝状态，导致静脉血栓栓塞风险增加。引发这种情况的机制之一是肿瘤产生组织因子（TF），并以与脂质结合的小微粒形式释放。我们之前已经证明，肿瘤细胞系培养基会诱导人脐静脉内皮细胞（HUVEC）出现促凝变化。本研究的目的是探究肿瘤微粒和重组人TF（rhTF）对内皮细胞的影响。通过超滤收集来自PANC - 1细胞系的促凝微粒。然后将HUVEC与这些促凝微粒或rhTF一起孵育。使用流式细胞术研究内皮细胞表面蛋白表达和微粒释放的影响。无细胞肿瘤培养基的促凝活性是由微粒而非可溶性TF引起的。我们还证明，暴露于肿瘤微粒会导致内皮微粒释放增加，呈现正线性关系（R = 0.6630，P≤0.0001）。rhTF未诱导出与微粒相关的任何变化。在此我们证明，肿瘤细胞系培养基的促凝活性取决于微粒，并且内皮细胞暴露于这些微粒会导致HUVEC释放的微粒增加。这提示了一种促凝潜能从癌症转移至远处内皮细胞的机制。
