Suppression of Breast Cancer Progression by Tissue Factor
Annual rept. 5 May 2003-4 May 2004
SCRIPPS RESEARCH INST LA JOLLA CA
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Tissue Factor TF is the cell surface receptor that activates coagulation by binding the serine protease coagulation factor VIIa VIIa. The activation of the coagulation cascade leads to thrombin generation, fibrin formation and platelet activation which together may aide tumor growth and metastasis. TF is released from tumor cells by shedding or TF comes in contact with coagulation factors when tumor cells enter the blood stream, leading to a hypercoagulable state and its clinical manifestation of spontaneous thrombosis Trousseaus Syndrome that occurs in several types of cancer. This provides clear evidence that TF is a frequent marker of advanced cancer. This project proposes to elucidate mechanisms that underlie the seemingly paradoxical observation that TF which supports metastasis under certain conditions may actually delay tumor development and local spread in breast cancer. The basic hypothesis pursued here is that the complex signaling functions of the TF cytoplasmic domain contribute to this paradox. We hope to discover new avenues to specifically interrupt breast cancer progression by unraveling the role of TF cytoplasmic domain signaling in cancer cells.
- Anatomy and Physiology
- Medicine and Medical Research