Glycosaminoglycans in human retinoblastoma cells: Heparan sulfate, a modulator of the pigment epithelium-derived factor-receptor interactions

BACKGROUND: Pigment epithelium-derived factor (PEDF) has binding affinity for cell-surface receptors in retinoblastoma cells and for glycosaminoglycans. We investigated the effects of glycosaminoglycans on PEDF-receptor interactions. RESULTS: (125)I-PEDF formed complexes with protease-resistant components of medium conditioned by human retinoblastoma Y-79 cells. Using specific glycosaminoglycan degrading enzymes in spectrophotometric assays and PEDF-affinity chromatography, we detected heparin and heparan sulfate-like glycosaminoglycans in the Y-79 conditioned media, which had binding affinity for PEDF. The Y-79 conditioned media significantly enhanced the binding of (125)I-PEDF to Y-79 cell-surface receptors. However, enzymatic and chemical depletion of sulfated glycosaminoglycans from the Y-79 cell cultures by heparitinase and chlorate treatments decreased the degree of (125)I-PEDF binding to cell-surface receptors. CONCLUSIONS: These data indicate that retinoblastoma cells secrete heparin/heparan sulfate with binding affinity for PEDF, which may be important in efficient cell-surface receptor binding.