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The notion that clotting proteins can serve more than one function (i.e., beyond their involvement in the production of a fibrin clot) is not new and is consistent with a broad view of biology that acknowledges the importance of redundant systems and overlapping functions for proteins to accomplish a variety of physiologic tasks. Indeed, thrombin, the ultimate clotting protease, is well-known as a mitogen for many cell types, acting as a growth-promoting stimulus for, among others, smooth muscle cells, endothelial cells, and, most recently, tumor cells.1 In this issue of Seminars in Thrombosis and Hemostasis, we are pleased to present a current view of the ubiquitous, transmembrane clotting protein tissue factor (TF) as a critical player in tumor biology; not just by virtue of its well-known properties as the receptor for factor VIIa–mediated triggering of both the intrinsic and extrinsic clotting cascades, but also as a signaling protein for the regulation of tumor cell movement, angiogenesis, and metastasis.
Rickles et al. (Sat,) studied this question.