Growth of human tumor cell lines in transferrin-free,low-iron medium |
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Authors: | Vera Neumannova Des R Richardson Karin Kriegerbeckova Jan Kovar |
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Institution: | (1) Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Videnska 1083, CS 142 20 Prague 4, Czech Republic;(2) Lady Davis Institute for Medical Research of the Sir-Mortimer B. Davis Jewish General Hospital, 3755 Chemin de la Cote-Ste-Catherine Road, H3T 1E2 Montreal, Quebec, Canada |
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Abstract: | 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 μM ferric 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. |
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Keywords: | low-iron medium transferrin-free medium tumor cell lines |
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