López-Pedrera C, Barbarroja N, Dorado G, Siendones E, Velasco F
Unidad de Investigación, Hospital Universitario Reina Sofía, Córdoba, Spain.
Leukemia. 2006 Aug;20(8):1331-40. doi: 10.1038/sj.leu.2404264. Epub 2006 May 25.
In the last few years, it has become clear that the processes of tumor angiogenesis, metastasis and invasiveness are highly dependent on components of the blood coagulation cascade. One of the key proteins in coagulation is tissue factor (TF). In addition, TF is also known as a mediator of intracellular signaling events that can alter gene expression patterns and cell behavior. TF significantly participates in tumor-associated angiogenesis and its expression levels have been correlated with the metastatic potential of many types of hematological malignancies. Signaling pathways initiated by both, tissue factor-activated factor VII (TF-FVIIa) protease activation of protein-activated receptors (PARs), and phosphorylation of the TF-cytoplasmic domain, appear to regulate these tumoral functions. Advances in antiangiogenic therapies and preclinical studies with TF-targeted therapeutics are hopeful in the control of tumor growth and metastasis, but continued studies on the regulation of TF are still needed. In the last few years, the use of approaches of functional genomics and proteomics has allowed the discovery of new proteins involved in the origin of the neoplasia and their participation in the development of the disease. This review attempts to establish a cellular and molecular causal link between cancer coagulopathy, angiogenesis and tumor progression in hematological malignancies.
在过去几年中，肿瘤血管生成、转移和侵袭过程高度依赖于凝血级联反应的成分这一点已变得清晰。凝血过程中的关键蛋白之一是组织因子（TF）。此外，TF还作为细胞内信号事件的介质为人所知，它能够改变基因表达模式和细胞行为。TF显著参与肿瘤相关血管生成，其表达水平与多种血液系统恶性肿瘤的转移潜能相关。由组织因子激活的因子VII（TF - FVIIa）蛋白酶激活蛋白激活受体（PARs）以及TF细胞质结构域的磷酸化所引发的信号通路，似乎对这些肿瘤功能起到调节作用。抗血管生成疗法和针对TF的治疗方法的临床前研究进展，为控制肿瘤生长和转移带来了希望，但仍需继续研究TF的调控机制。在过去几年中，功能基因组学和蛋白质组学方法的应用使得人们发现了参与肿瘤发生起源及其在疾病发展过程中发挥作用的新蛋白。本综述试图在血液系统恶性肿瘤的癌症凝血病、血管生成和肿瘤进展之间建立细胞和分子层面的因果联系。
