STRUCTURAL COMPARISON OF FIBROBLAST GROWTH FACTOR-SPECIFIC HEPARAN SULFATES DERIVED FROM A GROWING OR DIFFERENTIATING NEUROEPITHELIAL CELL-LINE

Heparan sulfate (HS) glycosaminoglycans are essential modulators of fi broblast growth factor (FGF) activity both in vivo and in vitro, and a ppear to act by cross-linking particular forms of FGF to appropriate F GF receptors, We have recently isolated and characterized two separate HS pools derived from immortalized embryonic day 10 mouse neuroepithe lial 2.3D cells: one from cells in log growth phase, which greatly pot entiates the activity of FGF-2, and the other from cells undergoing co ntact-inhibition and differentiation, which preferentially activates F GF-1. These two pools of HS have very similar functional activities to those species isolated from primary neuroepithelial cells at correspo nding stages of active proliferation or differentiation. We present he re a structural comparison between these cell line us species to estab lish the nature of the changes that occur in the biosynthesis of HS, A combination of chemical and enzymatic cleavage, low pressure chromato graphy and strong anion-exchange HPLC were used to generate full chain models of each species, Overall, the HS pools synthesized in the divi ding cell line pools possessed less complex sulfation than those deriv ed from more differentiated, growth arrested cells.