PRODUCTION AND ACTIVATION OF MATRIX METALLOPROTEASE-9 (MMP-9) BY HL-60 PROMYELOCYTIC LEUKEMIA-CELLS

Human promyelocytic HL-60 cells have been used as a model of acute leu kemia to investigate the expression and the regulation of matrix metal loproteases (MMPs), known to contribute to the degradation of extracel lular matrix components. As shown by gelatin zymography, HL-60 cells c onstitutively released significant amounts of proMMP-9 (92 kDa) and mo derate amounts of proMMP-2 (72 kDa). Furthermore, casein zymography co nfirmed the presence of serine proteases in the form of pro-urokinase. Activation of proMMP-9 was dependent on the plasminogen activator/pla smin (PA/plasmin) system and was inhibited by aprotinin. MMP-9 was onl y detected in cellular extracts or conditioned media incubated with HL -60 cells, indicating that cells are essential to the activation proce ss. Addition of plasminogen increased by 3-fold the basal invasive rat e of these cells across a matrigel layer (2.1% versus 0.7% in control cells after 4 h of incubation). Taken together, these results indicate that HL-60 cells exhibit an autocrine activation mechanism of proMMP- 9 via the PA/plasmin system and that activation of proMMP-9 increases their invasive potential. (C) 1997 Academic Press.