Establishment and characterization of a unique human cell line that proliferates dependently on GM-CSF, IL-3, or erythropoietin.
We have established a novel cell line, designated as TF-1, from a patient with erythroleukemia, which showed complete growth dependency on granulocyte-macrophage colony-stimulating factor (GM-CSF) or on interleukin-3 (IL-3) and carried a homogeneous chromosomal abnormality (54X). Erythropoietin (EPO) also sustained the short-term growth of TF-1, but did not induce erythroid differentiation. These three hematopoietic growth factors acted on TF-1 synergistically. Transforming growth factor-beta and interferons inhibited the factor-dependent growth of TF-1 cells in a dose-dependent fashion, and monocyte-colony stimulating factor and interkeukin-1 enhanced the GM-CSF-dependent growth of TF-1. Ultrastructural studies revealed some very immature features in this cell line. Although TF-1 cells do not express glycophorin A or carbonyl anhydrase I, the morphological and cytochemical features, and the constitutive expression of globin genes, indicate the commitment of TF-1 to erythroid lineage. When induced to differentiate, TF-1 entered two different pathways. Specifically, hemin and delta-aminolevulinic acid induced hemoglobin synthesis, whereas TPA induced dramatic differentiation of TF-1 into macrophage-like cells. In summary, TF-1 is a cell line of immature erythroid origin that requires GM-CSF, IL-3, or EPO for its growth and that has the ability to undergo differentiation into either more mature erythroid cells or into macrophage-like cells. TF-1 is a useful tool for analyzing the human receptors for IL-3, GM-CSF, and EPO or the signal transduction of these hemopoietic growth factors.
Kitamura
T
T
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Tange
T
T
Terasawa
T
T
Chiba
S
S
Kuwaki
T
T
Miyagawa
K
K
Piao
Y F
YF
Miyazono
K
K
Urabe
A
A
Takaku
F
F
D000328:Adult; D000954:Antigens, Surface / Q000032:analysis; D001853:Bone Marrow / Q000032:analysis / Q000187:drug effects / Q000473:pathology*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D004921:Erythropoietin / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology; D008297:Male; D008938:Mitosis; D013234:Stem Cells / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000032:analysis / Q000473:pathology
D000954:Antigens, Surface; D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007377:Interleukin-3; D004921:Erythropoietin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor