Membrane type-1
matrix metalloproteinase (MT1-MMP) has been implicated in
tumor invasion, as well as trafficking of normal hematopoietic cells, and acts as a physiologic activator of
proMMP-2. In this study we examined
MT1-MMP expression in primary
acute myeloid leukemia (AML) cells. Because
tumor necrosis factor (TNF)-α is known to be elevated in AML, we also investigated the effect of TNF-α on
MT1-MMP expression. We found (i)
MT1-MMP mRNA expression in 41 out of 43 primary AML samples tested; (ii) activation of
proMMP-2 in co-cultures of AML cells with normal bone marrow stromal cells; and (iii) inhibition of
proMMP-2 activation and trans-
Matrigel migration of AML cells by gene silencing using
MT1-MMP siRNA. Moreover, recombinant human TNF-α upregulated
MT1-MMP expression in AML cells resulting in enhanced
proMMP-2 activation and trans-
Matrigel migration. Thus, AML cells express
MT1-MMP and TNF-α enhances it leading to increased MMP-2 activation and most likely contributing to the invasive phenotype. We suggest that
MT1-MMP, together with TNF-α, should be investigated as potential therapeutic targets in AML.