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 micrograms/ml) or a higher concentration of ferric citrate (500 microM) 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 microM). 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 microM 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.

Institute of Molecular Genetics Academy of Sciences of the Czech Republic Prague 4 Czech Republic

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Biochim Biophys Acta. 1988 Apr 25;969(2):158-65 PubMed

Immunol Lett. 1984;7(6):339-45 PubMed

Cancer Res. 1985 Aug;45(8):3537-40 PubMed

Exp Cell Res. 1977 Feb;104(2):255-62 PubMed

Cancer Res. 1994 Feb 1;54(3):685-9 PubMed

J Clin Invest. 1985 Mar;75(3):1061-7 PubMed

J Biol Chem. 1990 Feb 25;265(6):3139-45 PubMed

J Biol Chem. 1989 Mar 15;264(8):4417-22 PubMed

J Biol Chem. 1983 Aug 10;258(15):9108-15 PubMed

In Vitro Cell Dev Biol. 1989 Jul;25(7):650-4 PubMed

J Immunol Methods. 1989 May 12;119(2):203-10 PubMed

Dig Dis Sci. 1980 May;25(5):340-6 PubMed

Folia Biol (Praha). 1985;31(2):167-75 PubMed

Can J Biochem. 1970 Dec;48(12):1339-50 PubMed

Anal Biochem. 1983 Apr 15;130(2):445-53 PubMed

J Biol Chem. 1988 Jun 25;263(18):8844-50 PubMed

Proc Natl Acad Sci U S A. 1982 Feb;79(4):1175-9 PubMed

Folia Biol (Praha). 1993;39(1):29-39 PubMed

Biochim Biophys Acta. 1991 Jun 7;1093(1):20-8 PubMed

Exp Cell Res. 1988 May;176(1):87-95 PubMed

Biochim Biophys Acta. 1981 Mar 20;642(1):119-34 PubMed

J Cell Physiol. 1982 Sep;112(3):403-10 PubMed

J Biol Chem. 1991 Feb 15;266(5):2997-3004 PubMed

Clin Sci (Lond). 1985 Apr;68(4):463-7 PubMed

Biochem Soc Symp. 1986;51:117-29 PubMed

J Immunol Methods. 1983 Dec 16;65(1-2):55-63 PubMed

Biochim Biophys Acta. 1990 Jun 12;1053(1):1-12 PubMed

J Membr Biol. 1985;88(3):205-15 PubMed

Blood. 1977 Sep;50(3):433-9 PubMed

Blood. 1991 Sep 15;78(6):1526-31 PubMed

Br J Haematol. 1987 Jun;66(2):149-51 PubMed

Proc Natl Acad Sci U S A. 1981 May;78(5):3039-43 PubMed

J Cell Physiol. 1984 Oct;121(1):251-6 PubMed

Cancer Res. 1987 Feb 15;47(4):936-42 PubMed

Hepatology. 1990 Sep;12(3 Pt 1):498-504 PubMed

Cancer Res. 1986 Apr;46(4 Pt 1):1644-7 PubMed

Exp Hematol. 1992 May;20(4):436-41 PubMed

J Clin Invest. 1988 Jul;82(1):331-9 PubMed

Immunol Cell Biol. 1993 Aug;71 ( Pt 4):303-9 PubMed

J Biol Chem. 1990 Apr 25;265(12):6688-92 PubMed

The inability of cells to grow in low iron correlates with increasing activity of their iron regulatory protein (IRP)