ANGIOSTATIN UP-REGULATES E-SELECTIN IN PROLIFERATING ENDOTHELIAL-CELLS

Angiostatin, a 38 kilodalton fragment of plasminogen, is a potent inhi bitor of angiogenesis. However, little is known about how angiostatin affects endothelial gene expression. To learn more about its effect on endothelial-specific genes implicated in angiogenesis, we examined E- selectin expression and function in bovine capillary endothelial cells treated with recombinant angiostatin. Angiostatin caused a four to fi ve-fold increase in E-selectin polypeptide levels in proliferating end othelial cells but little or no increase in confluent cells. P-selecti n polypeptide levels were unaffected by angiostatin in either prolifer ating or confluent cells. E-selectin mRNA and adhesion activity in pro liferating endothelial cells were also increased by angiostatin. Angio statin had little effect on the distribution of endothelial cells in G (0)/G(1), S, and G(2)/M, indicating angiostatin does not alter cell cy cle progression significantly. These data demonstrate that angiostatin selectively upregulates E-selectin in proliferating endothelial cells in vitro. This selectivity may provide insights into the mechanism by which angiostatin inhibits tumor growth in vivo without apparent effe cts on quiescent endothelium. (C) 1998 Academic Press.