Cellular effects of initiation of the extrinsic pathway of blood coagulation

In the initial phase of scientific research into blood clotting around 50 years ago most studies focused on investigating blood samples to find out what took place in the flowing blood. With the purification and cloning of Tissue Factor (TF) it was realized that TF was an integral membrane protein sitting in the cell surface membrane. This shifted the emphasis to investigations of what happened on the cell surface, and later to the cell biology of TF and its inducibility in monocytes/macrophages and endothelial cells. During the last 8 years, researchers have become increasingly interested in studying the processes going on inside the cells that carry TF when coagulation is initiated on their surface. Cells carrying TF have been incriminated in tumorigenesis, metastasis, angiogenesis,and a number of other cellular phenotypes. That binding of the plasma clotting Factor VIIa upregulates a number of genes involved in regulation of growth, transcription, and cellular motility, as well as cytokines, makes it possible to suggest a link between the formation of the TF/Factor VIIa complex and these cellular processes. (Trends Cardiovasc Med 2000;10:360-365). (C) 2001 Elsevier Science Inc.