Several laboratories have also demonstrated that the angiostatin-related peptides have inhibitory activity on the migration of endothelial
PaTrin 2 [14] and [23]. We confirmed the inhibitory activity of kringle domain-containing peptides on cell migration. Moreover, addition of PAP did not affect the inhibitory effects of K1–3, K1–4, and mini-Plg and these data are different from those obtained from the proliferation assay. PAP by itself slightly increased the migration of endothelial cells. However, PAP together with Lys-Plg stimulated endothelial cell migration. Thus in both proliferation and migration of endothelial cells, PAP showed distinct effect only with Lys-Plg but not with Glu-Plg and mini-Plg. In case of K1–3 and K1–4, PAP only affected the proliferation but not the migration of endothelial cells. These effects of PAP correlated well with the binding characteristics between PAP and the plasminogens as well as the kringle fragments. The reason why PAP affected the migration of endothelial
cells only when it was co-incubated with Lys-Plg and not with the angiostatin-related peptides is unclear. The interaction of PAP with Lys-Plg could induce a conformational change, which might not be the same as that of Glu-Plg, and this change might alter the properties of Lys-Plg and thus enhanced the activity of Lys-Plg on the proliferation and migration of endothelial cells.