Cell-to-cell interaction of cytokine-dependent myeloblastic line
constitutively expressing membrane-bound stem cell factor abrogates
cytokine dependency partially through granulocyte-macrophage colony-
stimulating factor production
K Sasaki, K Ikeda, K Ogami, J Takahara and S Irino
First Department of Internal Medicine, Kagawa Medical School, Japan.
Stem cell factor (SCF) is a cytokine for hematopoietic progenitor cells and
plays an important role in megakaryocyte proliferation. The UT-7 cell line
was established from a patient with megakaryoblastic leukemia, and its
growth and survival are strictly dependent on interleukin-3 (IL-3),
granulocyte-macrophage colony-stimulating factor (GM-CSF), erythropoietin
(Epo), or IL-6. In this study, we showed that SCF also supported the growth
of UT-7 in the absence of other cytokines and downregulated the cell
surface c-kit receptors. Constitutive expression of SCF by introducing SCF
expression vector made UT-7 grow factor-independently in liquid medium, but
not in semisolid medium. This SCF-expressing factor-independent UT-7
(UT-7scf9) expressed the membrane bound form of SCF on their surface, but
did not secrete detectable amounts of soluble SCF. UT-7scf9 formed
aggregates as they grew in the absence of cytokines, and this aggregation
was inhibited by adding soluble SCF into the medium. UT-7 cultured with SCF
and UT-7scf9 cultured without cytokines expressed GM-CSF, and anti-GM-CSF
neutralizing antibody partially inhibited their growth. These results
suggest that SCF stimulated UT-7 proliferation partially through the
autocrine-loop of GM-CSF, and UT-7scf9 expressed SCF mostly as a
membrane-bound form, which transduces its growth signal through c-kit
receptor as they aggregate by cell-to-cell interaction.
Volume 85,
Issue 5,
pp. 1220-1228,
03/01/1995
Copyright © 1995 by The American Society of Hematology
