Tissue factor pathway inhibitor seen as antiangiogenic agent
TFPI has a high degree of activity against endothelial cells, which are the building blocks of blood vessels, resulting in unique antiangiogenic properties. Coagulation is an important component of the metastatic spread of tumors, and by inhibiting both coagulation and angiogenesis this new finding uncovers the dual role of TFPI as a potential agent for cancer treatment.
Furthermore, EntreMed scientists believe that a newly discovered TFPI mechanism offers an important area of research for this and other angiogenesis inhibitor product candidates and further reinforces the link between blood coagulation and angiogenesis.
The article, "Tissue Factor Pathway Inhibitor Inhibits Endothelial Cell Proliferation Via Association with the Very Low Density Lipoprotein Receptor," by Hembrough, et al, was published today in the Journal of Biological Chemistry (JBC, Vol. 276, No. 15, pp. 12241-12248, 2001). The paper contains the following key findings reported for the first time:
- Tissue factor pathway inhibitor (TFPI), an endogenous anticoagulant molecule, specifically inhibits the growth of endothelial cells, which makes it an appropriate candidate for development as an antiangiogenic drug.
- The very low density lipoprotein (VLDL) receptor was identified as a novel receptor for TFPI which mediates TFPI's inhibitory activity on endothelial cells.
"This work identifies the VLDL receptor as an important regulator of endothelial cell growth, provides us with a novel target for the development of new antiangiogenic and antitumor drugs, and further expands Entremed's efforts into additional areas of angiogenesis research," says Edward R. Gubish, EntreMed's Executive Vice President for Research and Development.
"TFPI joins Endostatin, Angiostatin and Panzem™ in the list of naturally occurring antiangiogenic molecules that we are developing. We are currently evaluating several potential product candidates that have been identified through EntreMed's internal discovery program, including those identified through this pivotal research."
Dr. Dudley Strickland, Chairman of Vascular Biology at the Holland Research Laboratory of the American Red Cross, noted, "The discovery that the interaction of TFPI with the VLDL receptor regulates endothelial cell growth is an unexpected and exciting finding. This knowledge provides us with a new understanding of the fundamental processes underlying many diseases, including cancer and atherosclerosis."
Source: EntreMed, Inc.
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