GLYCOSAMINOGLYCANS ENHANCE PHORBOL ESTER-INDUCED PROTEOLYTIC ACTIVITYAND ANGIOGENESIS IN-VITRO

It has been reported that endothelial cells suspended in three-dimensi onal type I collagen gels can be induced to undergo tube formation by 12-o-tetradecanoyl phorbol 13-acetate (TPA). In this report, we show t hat TPA-induced endothelial cell tube formation can be further enhance d by the addition of other matrix components in the collagen gels. In the presence of TPA, both high molecular weight hyaluronate and chondr oitin sulfate elicit a dose-dependent stimulation of tube formation. T he enhanced tube formation appears to be due to an increase in the num ber of cells undergoing morphogenesis as the average length per tube i s not obviously increased. Concomitant with the increased cell morphog enesis, there is an increase in proteolytic activity secreted by the c ells. Treatment of cells with cycloheximide suppresses hyaluronate- an d chondroitin sulfate-enhanced cell morphogenesis and proteolytic acti vity suggesting that new protein synthesis, perhaps proteases, is nece ssary for endothelial cell morphogenesis. The possible role of the pro duction of proteolytic activity in endothelial cell tube formation is discussed.