Bruce Terman (Albert Einstein College of Medicine, Yeshiva University)
(November 4, 2003 2:30 PM - 3:30 PM)
Angiogenesis, the formation of new blood vessels, is required for several normal physiological process including development and wound healing. Angiogenesis also contributes to the progression of several diseases because it is a mechanism for providing diseased tissue with the nutrients required for cellular viability. For example, angiogenesis is required for tumors to grow beyond 1 mm in size. Pharmaceuticals that target angiogenesis block tumor growth in animal models and certain of these drugs are currently under clinical evaluation.
Angiogenesis is a complex physiological process that is mediated by the endothelial cells that form existing blood vessels. Component of this process include the degradation of the extracellular matrix, endothelial cell migration, cell proliferation, and vessel formation. These cellular activities are activated by extracellular stimuli, and both growth factors and the extracellular matrix regulate cell function. These activators do not enter the endothelial cells, but instead activate cell surface receptors triggering intracellular cell signal transduction pathways.
Vascular Endothelial Growth Factor (VEGF) has received considerable attention as a potent angiogenic growth factor. This is due in part to the observations that inhibition of VEGF function blocks both angiogenesis and tumor growth in animal models. VEGF binding to its high affinity receptor activates multiple signal transduction pathways and endothelial cell activities. Clarification of these signaling pathways may allow for the identification of new pharmaceutical targets and the development of more efficacious inhibitors.