Effect of short- or long-term treatment with exogenous glycosaminoglycans on growth and glycosaminoglycan synthesis of human fibroblasts (WI-38) in culture.

Short-term (several days) or long-term (several weeks and months) treatment of cultured human diploid fibroblasts (WI-38; phase II) with heparin at 20--500 micrograms/ml inhibited cell proliferation and stimulated glycosaminoglycan synthesis (as measured by the incorporation rates of [35S] sulfate and [14C] glucosamine into cellular and medium glycosaminoglycans). Characterization of the individual glycosaminoglycan types revealed an increased portion of incorporated radioactivity in the heparan sulfate and hyaluronic acid fractions of heparin-treated cells. Treatment with chondroitin-4-sulfate, chondroitin-6-sulfate, dermatan sulfate of hyaluronic acid at concentrations up to 500 micrograms/ml exhibited no or slightly inhibitory (especially in the case of hyaluronic acid) effects on growth and glycosaminoglycan synthesis. The average cellular protein and RNA content of short- or long-term heparin (100 micrograms/ml)-treated cells was elevated by about 70--80%. "Senescent" (phase III) WI-38 cells exhibited a relative increase of [35S] sulfate and [14C] glucosamine incorporation into cell-bound and medium heparan sulfate. Possible mechanisms for the action of heparin (for example, interaction with specific cell-surface sites) and a potential role of heparan sulfate in the regulation of cell growth are discussed.