Regulatory Effects of Cell Density on the Binding of Transforming Growth Factor β, Epidermal Growth Factor, Platelet-derived Growth Factor, and Fibroblast Growth Factor¹

The work described in this paper demonstrates that the cellular binding of transforming growth factor β, epidermal growth factor, platelet-derived growth factor, and fibroblast growth factor is reduced as cell density is increased. The reduction in transforming growth factor β binding was observed in five different cell lines. Examination of several of the cell lines, under conditions where transforming growth factor β binding is reduced, revealed that epidermal growth factor binding, platelet-derived growth factor binding, and fibroblast growth factor binding are also reduced. In the case of NRK-49F cells, the reduction in transforming growth factor β binding results from a decrease in the number of high-affinity receptors and not from a change in receptor affinity. Similarly, it was determined that the reduction in epidermal growth factor binding is due to a selective reduction in the high-affinity receptors for epidermal growth factor. Overall, the data suggest that the effect of cell density on growth factor binding, which we refer to as density-induced down regulation of growth factor receptors, differs both from down regulation induced by a specific growth factor and from receptor transmodulation.