ABSTRACT
Tissue factor (TF) is a transmembrane glycoprotein that initiates coagulation (1,2) and plays a critical role in regulating hemostasis and thrombosis (3,4). Human TF consists of three domains: a short cytoplasmic domain of 21 residues, a single transmembrane domain of 23 residues, and an extracellular domain of 219 residues. TF binds to factor (F) VIIa, and the resulting complex acts as a catalyst for the conversion of FIX and FX to FIXa and FXa, respectively, triggering the clotting cascade and leading to the generation of thrombin. Thrombin cleaves fi brinogen to fi brin, a major ingredient of thrombus. Thrombin is also a potent cell activator that has been implicated in infl ammation, growth, migration, and angiogenesis. TF is highly expressed in many tumors and in angiogenic endothelium, and it is inducible in vascular cells by many tumor-related agonists. TF expression is also
coupled to vascular endothelial growth factor (VEGF), a potent angiogenic factor. TF has been implicated in the thrombotic complications of cancer and in enhancing tumor growth, migration, metastasis, and angiogenesis. This chapter will summarize the multiple roles of TF in malignancy.
