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肿瘤形成评论综述™
SJR: 0.631 SNIP: 0.503 CiteScore™: 2

ISSN 打印: 0893-9675
ISSN 在线: 2162-6448

肿瘤形成评论综述™

DOI: 10.1615/CritRevOncog.2018024859
pages 219-248

The Role of Tissue Factor in Cancer-Related Hypercoagulability, Tumor Growth, Angiogenesis and Metastasis and Future Therapeutic Strategies

Patrick Van Dreden
Cancer Biology and Therapeutics, Centre de Recherche Saint-Antoine, INSERM U938, Institut Universitaire de Cancérologie (IUC), Faculté de Médecine, Sorbonne Universities, Paris, France; Clinical Research Department, Diagnostica Stago, Gennevilliers, France
Ιsmail Εlalamy
Cancer Biology and Therapeutics, Centre de Recherche Saint-Antoine, INSERM U938, Institut Universitaire de Cancérologie (IUC), Faculté de Médecine, Sorbonne Universities, Paris, France; Service d'Hématologie Biologique Hôpital Tenon, Hôpitaux Universitaires Est Parisien, Assistance Publique Hôpitaux de Paris
Grigoris T. Gerotziafas
Cancer Biology and Therapeutics, Centre de Recherche Saint-Antoine, INSERM U938, Institut Universitaire de Cancérologie (IUC), Faculté de Médecine, Sorbonne Universities, Paris, France; Service d'Hématologie Biologique Hôpital Tenon, Hôpitaux Universitaires Est Parisien, Assistance Publique Hôpitaux de Paris

ABSTRACT

It is widely recognized that a strong correlation exists between cancer and aberrant hemostasis. Patients with various types of cancers often develop thrombosis, a phenomenon commonly referred to as Trousseau syndrome. Tissue factor (TF) is expressed by tumor cells and contributes to a variety of pathologic processes, such as thrombosis, tumor growth, tumor angiogenesis, and metastasis. Tissue factor is expressed in two naturally occurring protein isoforms: membrane-bound full-length TF (flTF) and soluble alternatively spliced TF (asTF). Tissue factor is the primary initiator of blood coagulation, and it triggers intracellular signaling through protease-activated receptors (PARs). PARs are activated either by TF/FVIIa complexes or by thrombin generated following coagulation activation. Furthermore, the noncoagulant asTF retains an integrin-binding site and stimulates angiogenesis by ligating endothelial integrins αvβ3 and α6β1. Lastly, the increased TF expression in tumors is associated with the release in blood of TF-positive procoagulant microparticles that favor thromboembolic complications. Therefore, the interruption of asTF and flTF signaling represents a potential antiangiogenic strategy. In this review, we summarize the current knowledge on the role of TF in cancer, and we explore therapeutic perspectives based on TF targeting.