PDGF-BB INCREASES ENDOTHELIAL MIGRATION AND CORD MOVEMENTS DURING ANGIOGENESIS IN-VITRO

To explore direct effects of platelet-derived growth factor (PDGF) on endothelial cells during angiogenesis in vitro, we have used cloned bo vine aortic endothelial cells that spontaneously form cord structures. Recently we have shown that cells forming these endothelial cords exp ress PDGF beta-receptors and that PDGF-BB can contribute to cellular p roliferation and cord formation. In this study Lye investigated whethe r PDGF-induced cellular migration might also contribute to endothelial repair and angiogenesis in vitro. Ten individual endothelial cells in cords were tracked at an early stage of cord formation by video-timel apse microscopy. PDGF-BB (100 ng/ml) induced an increase in endothelia l cell movement of 67 +/- 15% as compared with diluent control. Intere stingly, PDGF-BB also increased movements of entire cord structures, f ollowed at branching points, by 53 +/- 12% over diluent control. Taken together, these video-timelapse experiments suggested that the appare nt movements of single endothelial cord cells might also be due to the motion of entire underlying cord structures in response to PDGF. To a nalyze the response of single endothelial cord cells we therefore exam ined whether PDGF-induced migration contributes to endothelial repair. Abrasions were applied with a razor blade to confluent monolayers of endothelial cells at an intermediate stage of cord formation. PDGF-BB concentration-dependently increased the distance to which cord-forming endothelial cells migrated into the abrasion. An increased number of elongated, i.e., probably migrating, endothelial cells was found in th e abrasion in response to PDGF-BB. However, there was no effect of PDG F-BB on the total number of endothelial cells found in the abrasion. P DGF-AA affected neither the distance to which the cells migrated nor t he number of elongated cells. Actin and tubulin stainings revealed tha t these cytoskeletal structures were not appreciably altered by PDGF-B B. Furthermore, urokinase-type plasminogen activator transcripts were not modulated in response to PDGF-BB. We conclude that in this model o f angiogenesis in vitro PDGF-BB can elicit the movement of entire cord structures, possibly via u-PA-independent mechanisms. PDGF-BB also co ntrols the migration of single cord-forming endothelial cells. Thus, P DGF-BB possibly contributes to endothelial repair and angiogenesis by direct effects on proliferation and composite movements of PDGF beta-r eceptor-expressing endothelial cells and cords. (C) 1997 Wiley-Liss, I nc.