Regulation and secretion of plasminogen activators and their inhibitors in
a human leukemic cell line (K562)
LJ Oliver, M Keeton and EL Wilson
Department of Cell Biology, New York University Medical Center 10016.
The secretion of tissue plasminogen activator (t-PA), urokinase (u-PA) and
their inhibitors by the human leukemia cell line K562 was examined. K562
cells normally secrete both t-PA and u-PA in a ratio of 3:1. After addition
of 10 or 1 ng/mL phorbol myristate acetate (PMA) to K562 cells, a marked
decrease in enzymatic activity is observed in the medium. However, when
t-PA antigen rather than activity is measured, an increased amount is found
in the medium under these conditions. PMA also induces secretion of the two
inhibitors of plasminogen activator: plasminogen activator inhibitor 1
(PAI-1) and plasminogen activator inhibitor 2 (PAI-2). This accounts for
the decrease in total enzymatic activity under conditions when production
of t-PA antigen is increased. A study of the time course of induction
revealed that the synthesis of plasminogen activator occurred before that
of its inhibitors. Low concentrations of PMA (0.1 ng/mL) induce t-PA
antigen primarily and not the inhibitors. This results in an increase in
total enzymatic activity, with 94% of the secreted activity being t-PA.
Thus, the secretion of plasminogen activators and their inhibitors can be
manipulated in certain leukemic cells by inducers such as PMA.
Volume 74,
Issue 4,
pp. 1321-1327,
09/01/1989
Copyright © 1989 by The American Society of Hematology
