Heparin Potentiates Endothelial Gell Growth Factor Stimulation of Plasminogen Activator Synthesis by Diploid Human Lung Fibroblasts

Endothelial cell growth factor (ECGF) stimulates the synthesis of t-PA and u-PA by confluent, diploid human lung fibroblasts, and this activity is potentiated considerably by heparin. In contrast, the malignant cell lines, Bowes melonoma and CALU-3, producers of t-PA and u-PA, respectively, are insensitive to ECGF. Studies with metabolic inhibitors and direct measurements of PA-specific mRNAs show that ECGF-mediated production of PA by human lung fibroblasts is dependent on de novo protein and RNA synthesis. The mechanism by which heparin potentiates this effect is thought to reside in its ability to prolong or strengthen the interaction of ECGF with cell surface receptors. The results raise the possibility that endogenous ECGF or related polypeptides (and heparin) may act to regulate PA synthesis by lung fibroblasts and possibly other responsive target cells in vivo.