THE 16-KILODALTON N-TERMINAL FRAGMENT OF HUMAN PROLACTIN IS A POTENT INHIBITOR OF ANGIOGENESIS

The formation of a new blood supply, angiogenesis, is an essential com ponent of carcinogenesis and unrestricted tumor growth. A substance ca pable of inhibiting angiogenesis would be of considerable therapeutic potential in the treatment of cancer. We previously reported that the 16-kilodalton N-terminal fragment of rat PRL (16K rPRL) was a potent i nhibitor of capillary endothelial cell proliferation via a novel recep tor. We now report that the nanomolar concentrations of recombinant hu man 16K PRL inhibit basal and basic fibroblast growth factor- or vascu lar endothelial growth factor-stimulated growth of bovine brain capill ary endothelial cells. 16K human (h) PRL also inhibits stimulation of human umbilical vein endothelial cell proliferation by basic fibroblas t growth factor. The organization of endothelial cells into capillary- like structures in type I collagen gels is also prevented by 16K hPRL. Furthermore, in an in vivo assay, the chick embryo chorioallantoic me mbrane assay, 16K hPRL as well as 16K rPRL were potent inhibitors of c apillary formation. 16K hPRL, like 16K rPRL, maintains its biological activity as a partial PRL agonist at PRL receptors on mammary gland ep ithelial cells. These data demonstrate for the first time that the bio logical activity of 16K rPRL is not unique and that similar fragments of hPRL are active. The antiangiogenic activity of these molecules is conserved across avian and mammalian species. That 16K hPRL is a poten t antiangiogenic factor in in vitro and an in vivo assay raises the ex citing potential of this peptide being capable of inhibiting tumor gro wth.