Department of Pathology and Laboratory Medicine, and.
Blood. 2013 Sep 12;122(11):1873-80. doi: 10.1182/blood-2013-04-460139. Epub 2013 Jun 24.
Patients with cancer have an increased risk for venous thrombosis. Interestingly, different cancer types have different rates of thrombosis, with pancreatic cancer having one of the highest rates. However, the mechanisms responsible for the increase in venous thrombosis in patients with cancer are not understood. Tissue factor (TF) is a transmembrane receptor and primary initiator of blood coagulation. Tumor cells express TF and spontaneously release TF-positive microparticles (MPs) into the blood. MPs are small membrane vesicles that are highly procoagulant. It has been proposed that these circulating tumor-derived, TF-positive MPs may explain the increased rates of venous thrombosis seen in patients with cancer. In animal models, increased levels of tumor-derived, TF-positive MPs are associated with activation of coagulation. Moreover, these MPs bind to sites of vascular injury and enhance thrombosis. We and others have found that patients with cancer have elevated levels of circulating TF-positive MPs. These MPs are derived from tumors because they express tumor markers and are decreased by tumor resection. Importantly, several studies have shown that increased levels of TF-positive MPs correlate with venous thrombosis in patients with cancer. Taken together, these results suggest that TF-positive MPs may be a useful biomarker to identify patients with cancer who are at high risk for thrombosis.
癌症患者发生静脉血栓的风险增加。有趣的是，不同类型的癌症发生血栓的几率不同，其中胰腺癌的血栓形成率最高。然而，导致癌症患者静脉血栓形成风险增加的机制尚不清楚。组织因子（TF）是一种跨膜受体，也是血液凝固的主要启动因子。肿瘤细胞表达 TF 并自发地将 TF 阳性微粒（MPs）释放到血液中。MPs 是一种小的膜囊泡，具有高度促凝作用。有人提出，这些循环肿瘤来源的 TF 阳性 MPs 可能解释了癌症患者中静脉血栓形成率增加的原因。在动物模型中，肿瘤来源的 TF 阳性 MPs 水平升高与凝血激活有关。此外，这些 MPs 与血管损伤部位结合并增强血栓形成。我们和其他人发现，癌症患者循环中 TF 阳性 MPs 的水平升高。这些 MPs 来源于肿瘤，因为它们表达肿瘤标志物，并通过肿瘤切除而减少。重要的是，几项研究表明，TF 阳性 MPs 水平升高与癌症患者的静脉血栓形成相关。综上所述，这些结果表明 TF 阳性 MPs 可能是一种有用的生物标志物，可用于识别有高血栓形成风险的癌症患者。
