Abstract
Ferritin has been reported to inhibit the growth of some leukemia cells in serum-supplemented culture. Recently we have found that ferritin stimulates the proliferation of human acute myeloblastic leukemia cells HL-60 and erythroleukemia cells K-562-T1 in serum-free medium. In this study, we examined the effect of ferritin against 14 human leukemia cell lines using human heart ferritin in serum-depleted culture medium. Among 14 cell lines tested, 10 were stimulated to proliferate by ferritin (maximum response at 30–300 ng/ml) with 0–1% fetal calf serum (FCS). The growth of all the cell lines was significantly inhibited by ferritin in the presence of 10% FCS. These results suggest that ferritin has dual functions; it promotes the growth of leukemia cells with low concentrations of FCS, but suppresses their growth with high concentrations of FCS.
Key words: Ferritin, Leukemia cells, Growth promotion, Growth inhibition, Serum concentration
Abbreviations
- FCS
fetal calf serum
- SDS-PAGE
sodium dodecyl sulfate/polyacrylamide gel electrophoresis
- PBS
Dulbecco's phosphate-buffered saline
- GM-CSF
granulocyte/macrophage-colony-stimulating factor
References
- Bellotti V, Arosio P, Cazzola M, Cozzi A, Levi S, Meloni F, Zappone E (1987) Characteristics of a ferritin-binding protein present in human serum. Br J Haematol 65: 489–493 [DOI] [PubMed] [Google Scholar]
- Bradford MMA (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Ann Biochem 72: 248–254 [DOI] [PubMed] [Google Scholar]
- Cazzola M, Arosio P, Bellotti V, Bergamaschi G, Dezza L, Iacobello C, Ruggeri G (1985) Use of a monoclonal antibody against human heart ferritin for evaluating acid ferritin concentration in human serum. Br J Hematol 61: 445–453 [DOI] [PubMed] [Google Scholar]
- Chiba S, Takaku F, Tange T, Shibuya K, Misawa C, Sasaki K, Miyagawa K, Yazaki Y, Hirai H (1991) Establishment and erythroid differentiation of a cytokine-dependent human leukemic cell line F-36: a parental line requiring granulocyte-macrophage colony-stimulating factor or interleukin-3, and a subline requiring erythropoietin. Blood 78: 2261–2268 [PubMed] [Google Scholar]
- Fargion S, Cappellini MD, Francanzani AL, Feo TMD, Levi S, Arosio P, Fiorelli G (1992) Binding and suppressive activity of human recombinant ferritins on erythroid cells. Am J Hematol 39: 264–268 [DOI] [PubMed] [Google Scholar]
- Giannoulis E, Arvanitakis C, Nikopoulos A, Dooutso I, Tourkantonis A (1984) Diagnostic value of serum ferritin in primary hepatocellular carcinoma. Digestion 30: 236–241 [DOI] [PubMed] [Google Scholar]
- Jacobs A, Jones B, Ricketts C, Bulbrook RD, Wang DY (1976) Serum ferritin concentration in early breast cancer. Br J Cancer 34: 286–290 [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kikyo N, Suda M, Kikyo N, Hagiwara K, Yasukawa K, Fujisawa M, Yazaki Y, Okabe T (1994) Purification and characterization of a cell growth factor from a human leukemia cell line: immunological identity with ferritin. Cancer Res 54: 268–271 [PubMed] [Google Scholar]
- Kitamura T, Tange T, Terasawa T, Chiba S, Kuwaki T, Miyagawa K, Piao Y-F, Miyazono K, Urabe A, Takaku F (1989) Establishment and characterization of a unique human cell line that proliferates dependently on GM-CSF, IL-3, or erythropoietin. J Cell Physiol 140: 323–334 [DOI] [PubMed] [Google Scholar]
- Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227: 680–685 [DOI] [PubMed] [Google Scholar]
- Mack U, Storey EL, Powell LW, Halliday JW (1985) Characterization of the binding of ferritin to the rat liver ferritin receptor. Biochim Biophys Acta 843: 164–170 [DOI] [PubMed] [Google Scholar]
- Maxim PE, Veltri RW, Davis MA (1982) Occurrence of ferritin-bound immune complexes in the sera of cancer patients and controls. Proc Am Assoc Cancer Res 23: 274 [Google Scholar]
- Moroz C, Bessler H, Lurie Y, Shaklai M (1987) New monoclonal antibody enzymoassay for the specific measurement of placental ferritin isotype in hematologic malignancies. Exp Hematol 15: 258–262 [PubMed] [Google Scholar]
- Sala G, Worwood M, Jacobs A (1986) The effect of isoferritin on granulopoiesis. Blood 67: 436–443 [PubMed] [Google Scholar]
- Yamada H, Gabuzda TG (1974) Interaction between rabbit erythroblast ferritin and normal plasma proteins. Blood 43: 875–883 [PubMed] [Google Scholar]
