Constitutive production of leukemia differentiation, colony-stimulating, erythroid burst-promoting, and pluripoietic factors by a human hepatoma cell line: characterization of the leukemia differentiation factor.
Conditioned medium (CM) obtained from a human hepatoma cell line, SK-HEP-1, contains colony-stimulating factors (CSFs) active on murine and human bone marrow-derived granulocyte and macrophage colony-forming units (CFU-GM) and a factor capable of inducing granulocyte-macrophage differentiation (GM-DF) of murine myelomonocytic leukemic cells WEHI-3B(D+) and human promyelocytic leukemic cells HL-60 when assayed in semisolid agar cultures. The human active granulocyte-macrophage colony-stimulating factor (GM-CSF) for day 7 CFU-GM and the GM-DF for WEHI-3B(D+) and for HL-60 are not separable by acrylamide agarose column chromatography, eluting at an apparent molecular weight between 20,000 and 35,000 daltons, or by isoelectric focusing (isoelectric point, pH 5.4). In addition, SK-HEP-1 CM contains erythroid burst-promoting activity (BPA) and a factor that promotes the growth of human mixed colonies. SK-HEP-1 cells, which grow as an adherent monolayer, appear not to be endothelial or monocytic in origin since by immunofluorescent staining they are negative for Ia (HLA-DR), monocyte antigen 1 and 2, lysozyme, and factor VIII-related antigen. Positive immunofluorescent staining for keratin and fibronectin suggests the possibility that SK-HEP-1 is an epithelial cell line. Constitutive production of GM-DF as well as other hematopoietic activities including GM-CSF, erythroid BPA, and an activity that promotes the growth of human mixed colony progenitors by a human epithelial tumor cell line, SK-HEP-1, suggests that this cell line is a valuable resource for both large-scale production of these factors and the cloning of the gene(s) that code for these regulators.
Gabrilove
J L
JL
Welte
K
K
Lu
L
L
Castro-Malaspina
H
H
Moore
M A
MA
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000096:biosynthesis*; D003470:Culture Media; D006023:Glycoproteins / Q000032:analysis / Q000096:biosynthesis*; D006098:Granulocytes / Q000473:pathology; D006131:Growth Inhibitors; D006801:Humans; D015850:Interleukin-6; D007525:Isoelectric Focusing; D053605:Leukemia Inhibitory Factor; D007942:Leukemia, Experimental; D008113:Liver Neoplasms / Q000378:metabolism*; D008222:Lymphokines; D008264:Macrophages / Q000473:pathology; D051379:Mice; D009504:Neutrophils / Q000473:pathology
D003115:Colony-Stimulating Factors; D003470:Culture Media; D006023:Glycoproteins; D006131:Growth Inhibitors; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines