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

Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68105

The work described in this paper demonstrates that the cellular binding of transforming growth factor ß, epidermal growth factor, platelet-derived growth factor, and fibroblast growth factor is reduced as cell density is increased. The reduction in transforming growth factor ß binding was observed in five different cell lines. Examination of several of the cell lines, under conditions where transforming growth factor ß 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 ß 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.

¹ Supported by grants from the Nebraska Department of Health (87-38), the National Institute of Child Health and Human Development (HD 19837), and the National Cancer Institute (Laboratory Cancer Research Center Support Grant CA 36727).

² To whom requests for reprints should be addressed.

Received 12/18/87. Revised 4/ 6/88. Accepted 5/ 4/88.

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