12-O-Tetradecanoylphorbol-13-acetate releases human diploid fibroblasts from contact-dependent inhibition of growth

Abstract
Treatment of human diploid fibroblasts at varying cell densities with 12-O-tetradecanoylphorbol-13-acetate (TPA) (10-7 M) resulted in a bimodal response of proliferation rate: while at low cell densities (3 .times. 103 - 1.5 .times. 104 cells/cm2) TPA inhibited the proliferation by up to 50%, at high cell densities (1 - 1.6 .times.105 cells/cm2) a 2-fold higher proliferation rate as in untreated cultures was observed. When sparsely seeded normal diploid fibroblasts were grown in the presence of immobilized plasma membrane glycoproteins, as in confluent cell cultres strongly decreased proliferation and enhanced collagen type III synthesis is found. Using this test system, it emerged that the addition of plasma membrane proteins from untreated as well as from TPA-treated fibroblasts to untreated fibroblasts resulted in a strong inhibition of proliferation rate. In contrast, the addition of either untreated or TPA-treated plasma membrane proteins to cells cultured in the presence of TPA had no effect on growth. It is suggested that TPA treatment of nromal diploid cells in culture results in a loss or responsiveness against cell-cell contacts, leading to an escape from the contact-dependent inhibition of growth.

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