The role of cell adhesion molecules in the formation of new blood vessels or angiogenesis has gained increasing attention in recent years. Cell adhesion molecules are thought to mediate an array of events during angiogenesis, from cell migration, to cell shape changes, interactions with extracellular matrix constituents, and capillary lumen formation. Our laboratory has focused on the role of E-selectin in angiogenesis. E-selectin is an endothelial cell-specific adhesion molecule first discovered because of its ability to mediate the binding of leukocytes to cytokine-activiated endothelial cells. Our studies, supported by the previous five years of this grant, have shown that E- selectin is required for bovine capillary endothelial cells to form capillary-like vessels in vitro. In addition, our recent work has shown the E-selectin is expressed in proliferating endothelial cells in vivo in three non-inflammed human tissues in which angiogenesis is occuring. In addition, we have shown that E-selectin is upregulated in vitro in subconfluent growing bovine capillary endothelial cells. Furthermore, E-selectin expression is increased in endothelial cells in G2/M phases of the cell cycle. These findings indicate that E-selectin can be regulated by both growth signals as well as by cytokine activation. The goals of this renewal application are elucidate the growth signals that regulate E-selectin expression and to examine how angiogenic inhibitors and stimulators affect this pathway. In addition, experiments are proposed to determine if E-selectin may be used to measure angiogenic potentioal of human tumors.
The specific aims are to1) identify growth signals that upregulate E-selectin expression in dividing endothelial cells, 2) to determine how angiogenic stimulators and inhibitors affect E-selectin expression, 3) to compare E-selectin- positive microvessel density to total microvessel density in human breast and prostate tumors to determine if E-selectin can be used to assess the angiogenic potential of human tumors.
Showing the most recent 10 out of 277 publications
