Basic fibroblast growth factor does not prevent heparan sulphate proteoglycan catabolism in intact cells, but it alters the distribution of the glycosaminoglycan degradation products

Heparan sulphate proteoglycans on cell surfaces have been shown to mediate the degradation or recycling of several ligands. Since the interaction with ligand may affect proteoglycan catabolism once the complex is internalized , this could alter the cellular pool of heparan sulphate chains, with possi ble consequences for heparan sulphate-mediated cellular processes. We have recently demonstrated that the specific binding of basic fibroblast growth factor (bFGF) to heparan sulphate chains prevents the glycosaminoglycan fro m being degraded by partially purified heparanases from Chinese hamster ova ry (CHO) cells [Tumova and Bame (1997) J, Biol. Chem. 272, 9078-9085]. The present study examines the effect of bFGF on heparan sulphate catabolism in intact cells. The distribution and size of the heparan sulphate degradatio n products in CHO cells was analysed in the presence and absence of bFGF us ing pulse-chase protocols. Although heparan sulphate molecules and bFGF are internalized through the same pathway, even relatively high concentrations of the growth factor do not have any inhibitory effects on glycosaminoglyc an degradation. However, the interaction with the growth factor alters the distribution of heparan sulphate-degradation products, presumably by preven ting secretion of the short heparanase-derived species. Our findings show t hat most of the free and bFGF-bound heparan sulphate chains are destined fo r lysosomes, which would be consistent with a recent hypothesis that the pr imary role of proteoglycan-mediated internalization of the growth factor is to remove bFGF from its site of action at the cell surface. However, in th e presence of bFGF, a fraction of intracellular, heparanase-degraded hepara n sulphate chains is delivered to the nucleus, suggesting that the glycosam inoglycan accompanies the growth factor to the organelle. It may be importa nt for bFGF activity that the growth factor is protected from proteolytic d egradation by its interaction with heparan sulphate. This work demonstrates that the internalization of a ligand along with the proteoglycan can affec t the sorting of heparan sulphate-degradation products in endosomes, and th e ultimate destination of the short glycosaminoglycan, It also provides evi dence that formation of heparan sulphate-ligand complexes may regulate the recycling and degradation of both ligands and heparan sulphate chains and, consequently, affect their biological activities.