Growth-regulative activity of human alpha-fetoprotein for different types of tumor and normal cells
Growth-regulative activity of human alpha-fetoprotein for different types of tumor and normal cells
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DOI：
10.1159/000029972
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发表时间：
1998-01-01
期刊：
影响因子：
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通讯作者：
Sukhikh, G
中科院分区：
文献类型：
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作者：
Dudich, E;Semenkova, L;Sukhikh, G
研究了不同类型肿瘤细胞和正常胚胎成纤维细胞（能够摄取甲胎蛋白（AFP））的剂量依赖性反应。高剂量（超过100 μ g/ml）的纯化人AFP显示出诱导强烈的剂量依赖性的人肝癌HepG 2细胞、人淋巴母细胞瘤MT4细胞、淋巴瘤Jurkat细胞和鼠成纤维细胞瘤L929细胞的生长抑制。人乳腺癌MCF-7细胞也显示出对AFP的生长抑制反应，尽管在较小程度上，等剂量的人血清白蛋白（HSA）对这些细胞没有影响。相反，不同器官来源的正常胚胎成纤维细胞对AFP的增殖反应呈剂量依赖性刺激（50-90%）。当用相同剂量的HSA处理胚胎成纤维细胞时，获得了类似的刺激效果。髓母细胞瘤细胞系U-937和正常表皮成纤维细胞系M19显示出在宽范围的蛋白浓度下对AFP作用具有抗性。结果表明，生长因子剥夺（即低血清浓度）可以刺激U-937细胞增殖，以响应高剂量的AFP。它还表明，密集清洗的U-937和MCF-7细胞与新鲜培养基，以消除分泌的细胞因子和生长因子显着增加细胞的敏感性，高剂量AFP诱导的生长抑制活性。低AFP浓度（低于100 μ g/ml）未能诱导所有研究细胞的生长抑制，而是显示出轻微的刺激作用。这些发现表明，生理水平的AFP可以对敏感的肿瘤或发育中的细胞表现出剂量依赖性的生长调节活性。我们的数据表明，AFP可以显示刺激或抑制生长活性，这取决于AFP的相对浓度和细胞培养基中的外源性或内源性细胞因子和生长因子，在正常胚胎成纤维细胞和某些肿瘤细胞系中由低浓度AFP表现出的生长刺激活性被认为是AFP和各种其他分泌的生长因子的协同作用的结果。
The dose-dependent alpha-fetoprotein (AFP) reactivity of different types of tumor cells and normal embryonal fibroblasts, which are capable of taking up AFP, was investigated. High doses (more than 100 mu g/ml) of purified human AFP were shown to induce strongly dose-dependent growth inhibition of human hepatoma HepG2 cells, human lymphoblastoma MT4 cells, lymphoma Jurkat cells and murine fibroblastoma L929 cells. Human mammary carcinoma MCF-7 cells also revealed a growth inhibitory response to AFP, although to a lesser extent, Equivalent doses of human serum albumin (HSA) demonstrated no effect on these cells. On the contrary, normal embryonal fibroblasts of different organ origin showed dose-dependent stimulation (50-90%) of proliferation in response to AFP. A similar stimulative effect was obtained when embryonal fibroblasts were treated with the same doses of HSA. The myeloblastoma cell line U-937 and the normal epidermal fibroblast cell line M19 were shown to be resistant to the AFP action over a wide range of protein concentrations. It was demonstrated that growth factor deprivation (i.e. low serum concentration) could stimulate U-937 cell proliferation in response to high doses of AFP. It was also shown that intensive washing of U-937 and MCF-7 cells with fresh medium to remove secreted cytokines and growth factors distinctly increased cell sensitivity to high-dose-AFP-induced growth-inhibitory activity. Low AFP concentrations (less than 100 mu g/ml) failed to induce growth inhibition in all studied cells and rather showed a slight stimulative effect. These findings demonstrate that physiological levels of AFP can exhibit a dose-dependent growth-regulatory activity toward sensitive tumor or developing cells, Our data demonstrated that AFP could reveal either stimulative or inhibitory growth activity, depending on the relative concentration of AFP and on exogenous or endogenous cytokines and growth factors in the cell culture medium, A growth-stimulative activity in normal embryonal fibroblasts and certain tumor cell lines exhibited by low AFP concentrations is supposed to result from the synergistic effects of AFP and various other secreted growth factors.