The effects of dexamethasone and tetradecanoyl phorbol acetate on
plasminogen activator release by human acute myeloid leukemia cells
EL Wilson, P Jacobs and EB Dowdle
This investigation was undertaken to examine the extent to which leukemic
cell functions are susceptible to regulation in vitro and to investigate
their heterogeneity in this regard. Since plasminogen activator release is
known to be a modulatable cellular function that can be influenced by
antiinflammatory steroids and tetradecanoyl phorbol acetate (TPA), the
effect of these two compounds on the secretion of urokinase- or tissue-type
enzymes by leukemic cells was studied. The release of both enzyme species
could be stimulated or suppressed by these substances by mechanisms that
were inhibitable by actinomycin-D and hence required transcription of new
mRNA. Plasminogen activator release by cells from 41/45 patients with AML
was either stimulated or inhibited by 10(-7) M dexamethasone, implying that
most AML cells possess glucocorticoid receptors. In 26/45 cases, the enzyme
was inhibited by this steroid to less than 25% of control values.
Pronounced inhibition of this degree was not encountered with normal
polymorphonuclear leukocytes. Plasminogen activator secretion by AML cells
was profoundly inhibited in 20/41 cases by 1 ng/ml TPA and stimulated in
8/41 cases. Leukemic blasts varied considerably in their response to
dexamethasone and TPA. Plasminogen activator release should prove a
sensitive means of monitoring the responses of AML cells to biologically
active compounds.
Volume 61,
Issue 3,
pp. 561-567,
03/01/1983
Copyright © 1983 by The American Society of Hematology
