Department of Thrombosis and Hemostasis, Einthoven Laboratory for Experimental Vascular Medicine, Leiden Univerisity Medical Center, Leiden, The Netherlands.
Blood. 2012 Jan 26;119(4):924-32. doi: 10.1182/blood-2011-06-317685. Epub 2011 Nov 7.
It is now widely recognized that a strong correlation exists between cancer and aberrant hemostasis. Patients with various types of cancers, including pancreatic, colorectal, and gastric cancer, often develop thrombosis, a phenomenon commonly referred to as Trousseau syndrome. Reciprocally, components from the coagulation cascade also influence cancer progression. The primary initiator of coagulation, the transmembrane receptor tissue factor (TF), has gained considerable attention as a determinant of tumor progression. On complex formation with its ligand, coagulation factor VIIa, TF influences protease-activated receptor-dependent tumor cell behavior, and regulates integrin function, which facilitate tumor angiogenesis both in vitro and in mouse models. Furthermore, evidence exists that an alternatively spliced isoform of TF also affects tumor growth and tumor angiogenesis. In patient material, TF expression and TF cytoplasmic domain phosphorylation correlate with disease outcome in many, but not in all, cancer subtypes, suggesting that TF-dependent signal transduction events are a potential target for therapeutic intervention in selected types of cancer. In this review, we summarize our current understanding of the role of TF in tumor growth and metastasis, and speculate on anticancer therapy by targeting TF.
现在人们普遍认识到，癌症与异常止血之间存在很强的相关性。患有各种类型癌症的患者，包括胰腺癌、结直肠癌和胃癌，常常会发生血栓形成，这种现象通常被称为特鲁索综合征。反过来，凝血级联反应的成分也会影响癌症的进展。凝血的主要启动子，跨膜受体组织因子（TF），已作为肿瘤进展的决定因素引起了相当大的关注。TF 与配体凝血因子 VIIa 形成复合物后，会影响蛋白酶激活受体依赖性肿瘤细胞行为，并调节整合素功能，从而促进体外和小鼠模型中的肿瘤血管生成。此外，有证据表明，TF 的一种选择性剪接同工型也会影响肿瘤生长和肿瘤血管生成。在患者标本中，TF 的表达和 TF 细胞质结构域磷酸化与许多但不是所有癌症亚型的疾病结局相关，这表明 TF 依赖的信号转导事件是针对选定类型癌症的治疗干预的潜在靶点。在这篇综述中，我们总结了我们目前对 TF 在肿瘤生长和转移中的作用的理解，并推测通过靶向 TF 进行抗癌治疗。
