Oesch F, Schäfer A, Wieser R J
Institut für Toxikologie, Johannes Gutenberg-Universität, Mainz, FRG.
Carcinogenesis. 1988 Jul;9(7):1319-22. doi: 10.1093/carcin/9.7.1319.
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 x 10(3)-1.5 x 10(4) cells/cm2) TPA inhibited the proliferation by up to 50%, at high cell densities (1-1.6 x 10(5) 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 cultures 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 cell cultured in the presence of TPA had no effect on growth. It is suggested that TPA treatment of normal diploid cells in culture results in a loss of responsiveness against cell-cell contacts, leading to an escape from the contact-dependent inhibition of growth.
用12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯（TPA）（10⁻⁷ M）在不同细胞密度下处理人二倍体成纤维细胞，导致增殖率出现双峰反应：在低细胞密度（3×10³ - 1.5×10⁴个细胞/cm²）时，TPA可使增殖抑制高达50%，而在高细胞密度（1 - 1.6×10⁵个细胞/cm²）时，观察到增殖率比未处理培养物高2倍。当稀疏接种的正常二倍体成纤维细胞在固定化质膜糖蛋白存在下生长时，如同在汇合细胞培养物中一样，会发现增殖强烈降低且III型胶原合成增强。使用该测试系统发现，将未处理以及TPA处理的成纤维细胞的质膜蛋白添加到未处理的成纤维细胞中会导致增殖率受到强烈抑制。相反，将未处理或TPA处理的质膜蛋白添加到在TPA存在下培养的细胞中对生长没有影响。有人提出，在培养中用TPA处理正常二倍体细胞会导致对细胞 - 细胞接触的反应性丧失，从而导致逃避接触依赖性生长抑制。
