CHANGES IN GLYCOSAMINOGLYCAN STRUCTURE AND COMPOSITION OF THE MAIN HEPARAN-SULFATE PROTEOGLYCAN FROM HUMAN COLON-CARCINOMA CELLS (PERLECAN)DURING CELL-DIFFERENTIATION

Colon carcinoma cells provide a useful model to study the biochemical processes associated with cell differentiation. Undifferentiated HT29, differentiated HT29MTX(-3) and HT29MTX(-6), and Caco2 human colon car cinoma cells have been used to study the production of proteoglycans a nd to characterize the glycosaminoglycan structure of the heparan sulp hate chains. All the cell lines produce mainly a heparan sulphate prot eoglycan that is found partly in the extracellular medium and associat ed to the cell membrane. The heparan sulphate proteoglycans from the m edia were purified by ion-exchange chromatography and subjected to str uctural analysis. The heparan sulphate proteoglycan from differentiate d cells is larger and more homogeneous in size than the heparan sulpha te proteoglycan from undifferentiated HT29 cells. No differences in pr otein core structure were observed when cells were labeled with [S-35] methionine and the protein cores visualized by gel electrophoresis. Ne vertheless, differences in glycosaminoglycan composition were found co rrelated with the degree of differentiation. The heparan sulphate chai ns from differentiated HT29MTX(-3) and HT29MTX(-6) cells have a higher sulphation degree than those from undifferentiated HT29 cells. The he paran sulphate from Caco2 cells is the most highly sulphated species. The differences are mainly attributed to O-sulphate groups. The increa se in O-sulphation was more pronounced for D-glucosamine 6-O-sulphate than for L-iduronic acid 2-O-sulphate groups.