Murine myeloid cells transformed by myb require fibroblast-derived or
autocrine growth factors in addition to granulocyte-macrophage colony-
stimulating factor for proliferation
EM Macmillan and TJ Gonda
Hanson Centre for Cancer Research, Institute of Medical and Veterinary
Science, Adelaide, Australia.
Murine myeloid cells can be transformed in vitro by infection with
recombinant retroviruses carrying activated myb genes. While these myb-
transformed hematopoietic cells (MTHCs) can proliferate continuously in
culture, they exhibit several characteristics of progenitor cells of the
granulocyte-macrophage (GM) lineage, including an absolute dependence on
hematopoietic growth factors (HGFs) such as GM colony- stimulating factor
(GM-CSF) for survival and growth. Whereas we have previously shown that
MTHCs respond synergistically to certain combinations of HGFs, we report
here that MTHCs apparently require two HGFs for proliferation, because
GM-CSF alone appears insufficient to promote growth when MTHCs are cultured
at very low densities. However, proliferation can be stimulated by either
increasing the density at which MTHCs are cultured (implying the production
of an autocrine growth factor) or by the presence of a feeder layer of
irradiated fibroblasts. We find that the activity of such feeder layers is
greatest when the MTHCs are allowed to contact them directly; and by using
mutant fibroblast lines, that it depends on the production of CSF- 1, but
not Steel factor (SLF). In contrast, the autocrine factor appears not to be
either CSF-1 or SLF, and the possibility is raised that it may represent a
novel HGF activity. Potential implications of these results for normal and
leukemic hematopoiesis are discussed.
Volume 83,
Issue 1,
pp. 209-216,
01/01/1994
Copyright © 1994 by The American Society of Hematology
