Unstimulated human acute myelogenous leukemia blasts secrete matrix metalloproteinases.

PURPOSE: 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. METHODS AND
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.