Growth of human tumor cell lines in transferrin-free, low-iron medium
Growth of human tumor cell lines in transferrin-free, low-iron medium
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DOI：
10.1007/bf02634316
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发表时间：
1995-09
期刊：
影响因子：
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通讯作者：
V. Neumannová;D. Richardson;K. Kriegerbecková;J. Kovar
中科院分区：
文献类型：
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作者：
V. Neumannová;D. Richardson;K. Kriegerbecková;J. Kovar
铁对肿瘤细胞生长至关重要。先前的研究已经证明，除了转铁蛋白结合的铁摄取之外，哺乳动物细胞还具有能够从小分子量铁螯合物有效获得铁的转运系统（Sturrock等人，1990年）。在本研究中，我们研究了肿瘤细胞在低分子量柠檬酸铁螯合物存在下生长的能力。在化学成分确定的无血清培养基中，大多数人类肿瘤细胞系需要转铁蛋白（5 µg/ml）或更高浓度的柠檬酸铁（500 µM）作为铁源。然而，我们还发现，从13个测试的人类细胞系中，有4个能够在无转铁蛋白的培养基中长期生长，其中柠檬酸铁浓度显著较低（5 µM）。当在含有转铁蛋白的培养基中生长时，常规和低铁依赖性细胞系都使用转铁蛋白结合的铁。运铁蛋白培养基中的两种细胞类型的生长在一定程度上被单克隆抗体42/6抑制，其特异性地阻断运铁蛋白与运铁蛋白受体的结合。相反，单克隆抗体42/6不能抑制低铁依赖性细胞系在无转铁蛋白、低铁培养基（5 µ M柠檬酸铁）中的生长。此外，没有观察到转铁蛋白的自分泌产生。低铁依赖性细胞系仍然对铁缺乏敏感，因为铁（III）螯合剂去铁胺抑制了它们的生长。我们的结论是，低铁依赖性肿瘤细胞在转铁蛋白，低铁介质中可能采用一种以前未知的机制摄取非转铁蛋白结合铁，使他们能够有效地利用低浓度的柠檬酸铁作为铁源。结果进行了讨论的背景下，替代铁的吸收机制，以及表征受体介导的内吞作用的过程。
Iron is essential for tumor cell growth. Previous studies have demonstrated that apart from transferrin-bound iron uptake, mammalian cells also possess a transport system capable of efficiently obtaining iron from small molecular weight iron chelates (Sturrock et al., 1990). In the present study, we have examined the ability of tumor cells to grow in the presence of low molecular weight iron chelates of citrate. In chemically defined serum-free medium, most human tumor cell lines required either transferrin (5 µg/ml) or a higher concentration of ferric citrate (500 µM) as an iron source. However, we have also found that from 13 human cell lines tested, 4 were capable of long-term growth in transferrin-free medium with a substantially lower concentration of ferric citrate (5 µM). When grown in medium containing transferrin, both regular and low-iron dependent cell lines use transferrin-bound iron. Growth of both cell types in transferrin medium was inhibited to a certain degree by monoclonal antibody 42/6, which specifically blocks the binding of transferrin to the transferrin receptor. On the contrary, growth of low-iron dependent cell lines in transferrin-free, low-iron medium (5 µMferric citrate) could not be inhibited by monoclonal antibody 42/6. Furthermore, no autocrine production of transferrin was observed. Low-iron dependent cell lines still remain sensitive to iron depletion as the iron(III) chelator, desferrioxamine, inhibited their growth. We conclude that low-iron dependent tumor cells in transferrin-free, low-iron medium may employ a previously unknown mechanism for uptake of non-transferrin-bound iron that allows them to efficiently use low concentrations of ferric citrate as an iron source. The results are discussed in the context of alternative iron uptake mechanisms to the well-characterized receptor-mediated endocytosis process.