The embryonic angiogenic factor Del1 accelerates tumor growth by enhancing vascular formation

Dell is a unique alphavbeta3 integrin ligand that is produced by endothelial cells, and thus provides an autocrine signaling pathway in this cell type. It is expressed transiently in the embryo and mediates cell attachment, migration, and activation of cytoplasmic signaling molecules in focal contacts. Dell also activates angiogenesis in the chick chorioallantoic membrane assay. Reexpression of this embryonic signaling molecule has now been documented in naturally occurring human tumors, where it is expressed by both tumor cells and angiogenic endothelial cells, suggesting that Dell is important in mediating angiogenesis under pathophysiological conditions in the adult. To investigate the role of Dell in tumor growth and angiogenesis, human 143B osteosarcoma cells and murine Lewis lung carcinoma cells were engineered to express Dell and compared to control transfectants for their ability to produce tumors in nude or syngeneic mice, respectively. Dell expressing tumors showed a two- to fourfold increase in capillary density and an accelerated rate of growth. Expression of Dell also correlated with a decrease in apoptosis in tumor cells in vivo. Taken together, these data suggest that Dell acts as an angiogenic factor in the context of solid tumor formation and that this increase in vascularization accelerates tumor growth through decreased apoptosis. (C) 2002 Elsevier Science (USA).