Unstimulated human acute myelogenous leukemia blasts secrete matrix metalloproteinases.
OBJECTIVE
The secretion of metalloproteinases was examined, especially the 92-kDa and 72-kDa type IV collagenases/gelatinases, and their role in the degradation of reconstituted basement membrane (Matrigel) by leukemic blasts.


RESULTS
Leukemic blasts were obtained from the peripheral blood of 11 patients diagnosed with acute myelogenous leukemia (AML). After incubation of the AML blasts in serum-free cultures, conditioned media were collected and examined by zymography. The 92-kDa gelatinase was detected in ten AML patients after 2 h and 24 h of incubation, and in five samples its activated form (83 kDa) was observed. 72-kDa gelatinase was detected in cell-conditioned media from four patients after 2 h and in media from ten patients after 24 h. Its activated forms (64-60 kDa) were observed in one of four samples after 2 h and in five of ten after 24 h. By contrast, normal peripheral mononuclear cells from healthy donors secreted only 92-kDa gelatinase after 24 h; the 72 kDa enzyme was not detectable. A specific inhibitor of metalloproteinases, 1,10-phenanthroline, significantly reduced the in vitro invasion of AML blasts in a Matrigel assay and completely inhibited gelatinolytic activity in zymography.


CONCLUSIONS
We concluded that primary, unstimulated peripheral-blood AML blasts secrete metalloproteinases, which may contribute to the in vitro degradation of reconstituted basement membrane.
Matsuzaki
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Department of Medicine, University of Alberta, Edmonton, Canada.
Janowska-Wieczorek
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D000328:Adult; D000368:Aged; D001485:Basement Membrane / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D017364:Collagenases / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004338:Drug Combinations; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D018093:Gelatinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D007797:Laminin / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology*; D008297:Male; D009361:Neoplasm Invasiveness; D010618:Phenanthrolines / Q000494:pharmacology; D011509:Proteoglycans / Q000378:metabolism
D015853:Cysteine Proteinase Inhibitors; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D007797:Laminin; D010618:Phenanthrolines; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D017364:Collagenases; D018093:Gelatinases; C025205:1,10-phenanthroline