Fernandez Patricia M, Patierno Steven R, Rickles Frederick R
Department of Pharmacology, George Washington University Medical Center, Washington, DC, USA.
Semin Thromb Hemost. 2004 Feb;30(1):31-44. doi: 10.1055/s-2004-822969.
The hypercoagulability exhibited by most cancer patients leads to serious complications such as venous thromboembolism and contributes to the pathogenesis of tumor growth and metastasis by promoting angiogenesis. The key player in this vicious cycle is tissue factor (TF), the initiator of blood coagulation. Although TF normally safeguards vascular integrity by inducing hemostasis upon injury, abnormal expression of TF in different tumors and related vascular endothelial cells contributes to unnecessary clot formation in cancer patients. Clotting-dependent induction of tumor angiogenesis is primarily mediated by TF-induced generation of thrombin and subsequent deposition of cross-linked fibrin. A cross-linked fibrin network provides a provisional proangiogenic matrix that facilitates blood vessel infiltration. Clotting-independent mechanisms of TF-induced tumor angiogenesis have also been described, mediated primarily by the cytoplasmic tail of the TF receptor. TF activation could contribute to the venous thromboembolism that has been reported as a complication of the use of novel antiangiogenic agents in combination with chemotherapy. Anticoagulants, such as low-molecular-weight heparin, may act to prevent these complications both by interfering with TF-mediated activation of clotting and by directly down-regulating angiogenesis. Thus, TF may prove to be a novel target for cancer therapy.
大多数癌症患者表现出的高凝状态会导致严重并发症，如静脉血栓栓塞，并通过促进血管生成促进肿瘤生长和转移的发病机制。这个恶性循环中的关键因素是组织因子（TF），即血液凝固的启动因子。虽然TF通常通过在损伤时诱导止血来保护血管完整性，但TF在不同肿瘤和相关血管内皮细胞中的异常表达会导致癌症患者形成不必要的血栓。凝血依赖性肿瘤血管生成主要由TF诱导的凝血酶生成和随后交联纤维蛋白的沉积介导。交联纤维蛋白网络提供了一个临时的促血管生成基质，便于血管浸润。也有TF诱导肿瘤血管生成的非凝血依赖性机制的描述，主要由TF受体的细胞质尾巴介导。TF激活可能导致静脉血栓栓塞，这已被报道为新型抗血管生成药物与化疗联合使用的并发症。抗凝剂，如低分子量肝素，可能通过干扰TF介导的凝血激活和直接下调血管生成来预防这些并发症。因此，TF可能被证明是癌症治疗的一个新靶点。
