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 leukemia to investigate the expression and the regulation of matrix metalloproteases (MMPs), known to contribute to the degradation of extracellular matrix components. As shown by gelatin zymography, HL-60 cells constitutively released significant amounts of proMMP-9 (92 kDa) and moderate amounts of proMMP-2 (72 kDa). Furthermore, casein zymography confirmed the presence of serine proteases in the form of pro-urokinase. Activation of proMMP-9 was dependent on the plasminogen activator/plasmin (PA/plasmin) system and was inhibited by aprotinin. MMP-9 was only detected in cellular extracts or conditioned media incubated with HL-60 cells, indicating that cells are essential to the activation process. Addition of plasminogen increased by 3-fold the basal invasive rate 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.
Devy
L
L
Laboratoire de Biochimie, Faculté de Pharmacie, Université de Reims Champagne-Ardenne, IFR 53, France.
Noël
A
A
Baramova
E
E
Bajou
K
K
Trentesaux
C
C
Jardillier
J C
JC
Foidart
J M
JM
Jeannesson
P
P
D007611:Aprotinin / Q000494:pharmacology; D017364:Collagenases / Q000096:biosynthesis* / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004792:Enzyme Precursors / Q000378:metabolism; D005780:Gelatin / Q000378:metabolism; D018922:HL-60 Cells / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000201:enzymology / Q000473:pathology; D020780:Matrix Metalloproteinase 9; D009361:Neoplasm Invasiveness; D010958:Plasminogen / Q000494:pharmacology; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D004792:Enzyme Precursors; D005780:Gelatin; D010958:Plasminogen; D007611:Aprotinin; D014568:Urokinase-Type Plasminogen Activator; D017364:Collagenases; D020780:Matrix Metalloproteinase 9