HEPARAN-SULFATE PROTEOGLYCAN AND CONTROL OF CELL-PROLIFERATION - ENHANCED SYNTHESIS INDUCED BY PHORBOL ESTER (PMA) DURING G(1)-PHASE

The effect of phorbol 12-myristate-13-acetate (PMA), a tumor-promoting phorbol ester, on the synthesis of proteoglycans of endothelial cells in culture was investigated. This phorbol activates protein kinase C (PKC) when added to cells in culture. PKC, in turn, modulates the acti vity of growth factors. Using [S-35]-sulfate or [H-3]-glucosamine to l abel the proteoglycans we have observed a 4-24-fold increase of the he paran sulfate (HS) synthesis in a dose-dependent manner (0-100 ng/ml). Chondroitin sulfate (CS) synthesis was not affected by PMA. The effec t of PMA could be completely abolished by a calcium ionophore (A23187) . By the use of synchronized cells and PMA pulses at different periods of the cell cycle, as well as [H-3]-thymidine incorporation, we were able to show that the enhancement of heparan sulfate synthesis is most prominent during G(1). Our data suggest that the release of HS to the medium could be one of the responses of the cell to a mitogenic stimu lus.