Cancer and Blood Diseases Institute, The Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, Ohio.
Semin Thromb Hemost. 2019 Sep;45(6):559-568. doi: 10.1055/s-0039-1693472. Epub 2019 Aug 5.
Pathological activation of the coagulation system occurs with virtually all forms of cancer, particularly epithelial malignancies. Accordingly, thrombosis is one of the most common comorbidities associated with cancer. Indeed, cancer-associated thromboembolism is the second leading cause of death for cancer patients, second only to the cancer itself. The identification of specific molecular mechanisms whereby tumor cells activate the coagulation system and drive thrombosis has been an active area of investigation for several decades. Studies in animal models and human trials have revealed that there is a bidirectional relationship between coagulation factor activity and cancer, whereby the pathological hemostatic system activation associated with cancer not only promotes thromboembolism but also drives progression of the malignancy. Numerous studies indicate that factors up and down the clotting cascade can contribute to various stages of cancer, including tumorigenesis, primary tumor growth, and metastasis. Although there are some mechanistic points of commonality, there are also clearly context-dependent contributions of coagulation components to cancer progression dependent on the type of cancer and stage of disease. It is also notable that in some instances, coagulation factors appear to contribute to cancer progression independently of their traditional roles in hemostasis and thrombosis. Here, the authors review the current state of the field with regard to hemostatic factor-driven cancer pathogenesis.
凝血系统的病理性激活几乎发生于所有类型的癌症，尤其是上皮性恶性肿瘤。因此，血栓形成是与癌症相关的最常见合并症之一。实际上，癌症相关性血栓栓塞症是癌症患者的第二大死亡原因，仅次于癌症本身。几十年来，研究人员一直致力于寻找肿瘤细胞激活凝血系统并导致血栓形成的特定分子机制。动物模型研究和人类临床试验表明，凝血因子活性与癌症之间存在双向关系，即与癌症相关的病理性止血系统激活不仅会促进血栓栓塞形成，还会促进恶性肿瘤的进展。大量研究表明，凝血级联反应中的各种因子都可能参与癌症的各个阶段，包括肿瘤发生、原发肿瘤生长和转移。尽管存在一些共同的机制要点，但凝血成分对癌症进展的贡献显然取决于癌症的类型和疾病阶段，具有明显的上下文依赖性。值得注意的是，在某些情况下，凝血因子似乎独立于其在止血和血栓形成中的传统作用，促进癌症的进展。在此，作者综述了目前在止血因子驱动的癌症发病机制方面的研究现状。
