Enhanced mitogenic responsiveness to granulocyte-macrophage colony-stimulating factor in HL-60 promyelocytic leukemia cells upon induction of differentiation.
Treatment of HL-60 leukemia cells with the inducers of differentiation dimethyl sulfoxide (DMSO) and 6-thioguanine (TG) reduces the proliferative capacity of the cells. DMSO acted in a serum-independent manner and reversibly inhibited competence to enter S phase after 24 h of treatment. Purified human granulocyte-macrophage colony-stimulating factor (GM-CSF) but not human CSF-1, restored S phase competence and growth of DMSO-treated cells over a 7-day period. GM-CSF had no effect on the saturation density of control cells, even under conditions of reduced growth. Furthermore, GM-CSF antagonized the growth inhibitory actions of TG associated with cytodifferentiation but not those associated solely with TG cytotoxicity. The number of high affinity, cell surface GM-CSF receptors doubled after treatment of HL-60 cells with DMSO for 24 h and reached a maximum 4- to 5-fold increase within 72 h of exposure. The Kd of GM-CSF binding, 240 pM, was comparable to the concentration required to elicit a mitogenic response in DMSO-treated cells. An HL-60 variant that had been selected for resistance to TG-induced growth inhibition and differentiation (R. E. Gallagher et al., Cancer Res., 44: 2642-2653, 1984) was found to have less than 20% of the cell surface GM-CSF receptors when compared to either wild type cells, or a variant line selected for resistance to TG cytotoxicity. These studies demonstrate that HL-60 cells undergoing differentiation simultaneously lose autonomous growth properties and acquire cell surface growth factor receptors and mitogenic responsiveness.
Schwartz
E L
EL
Department of Oncology, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, New York 10467.
Maher
A M
AM
D001790:Blood Physiological Phenomena; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D011956:Receptors, Cell Surface / Q000032:analysis; D016184:Receptors, Colony-Stimulating Factor; D013866:Thioguanine / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D011956:Receptors, Cell Surface; D016184:Receptors, Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D004247:DNA; D013866:Thioguanine; D004121:Dimethyl Sulfoxide