THE INSULIN-LIKE GROWTH-FACTOR II MANNOSE 6-PHOSPHATE RECEPTOR IS REQUIRED FOR PROLIFERIN-INDUCED ANGIOGENESIS/

Proliferin stimulates endothelial cell migration in culture and neovas cularization in vivo. Previous studies have demonstrated that prolifer in can bind to the insulin-like growth factor II/mannose 6-phosphate r eceptor, and that binding can be blocked by mannose 6-phosphate. We ha ve now found that this receptor plays an essential role in proliferin- induced angiogenesis. Proliferin binding to endothelial cells is block ed by the addition of mannose 6-phosphate, as is the ability of both r ecombinant and placental-derived proliferin to stimulate the migration of capillary endothelial cells in vitro and to induce neovascularizat ion in the rat cornea. Consistent with a direct role of this receptor in angiogenesis, insulin-like growth factor II, as well as a mutant fo rm of insulin-like growth factor II that binds to the insulin-like gro wth factor II/mannose 6-phosphate receptor but not to the insulin-like growth factor I receptor, also stimulate endothelial cell migration a nd neovascularization.