Control of Transformation and Invasiveness of Breast Cancer Cells by Estrogen Regulation of Proteinase Inhibitor 9
Abstract
Coagulation factor VIIa, a circulating serine protease, binds to its cofactor, tissue factor (TF), to trigger the blood clotting cascade. TF is a glycoprotein present on the surface of a variety of cell types found outside of the vasculature, and on various types of cancer cells. TF:VIIa complex formation ultimately leads to fibrin polymerization and platelet activation, in both normal states and thrombotic disease. Complex formation has also been shown to activate certain signaling cascades, altering cellular properties such as adhesion, migration, and potential for apoptosis. Many types of cancer cells have been shown to express high levels of TF. Blockage with anti-TF antibodies has demonstrated that metastasis depends on the presence of catalytically competent TF:VIIa complexes. Such cellular alterations, the high morbidity associated with thrombosis, and the privileged position of VIIa in the coagulation cascade, make inhibition of TF:VIIa an important issue in cancer therapy. We have demonstrated that antithrombin (AT) can inhibit TF:VIIa, when in the presence of heparin, and AT:VIIa complexes have been detected in plasma, suggesting that Vila is inhibited by AT in vivo. We have also shown that vitronectin enhances AT activity, and hence, VIIa inhibition, and that AT can reversibly inhibit VIIa in vitro.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2003
- Accession Number
- ADA423310
Entities
People
- Francesca C. Antonaci
Organizations
- University of Illinois Urbana–Champaign