title: Membrane Type-1 Matrix Metalloproteinase Expression in Acute Myeloid Leukemia and Its Upregulation by Tumor Necrosis Factor-α.
abstract: 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.
authors.affiliation: Canadian Blood Services R&D, Edmonton, Alberta T6G 2R8, Canada. anna.janowska@blood.ca.
authors.forename: Leah A
authors.initials: LA
authors.lastname: Marquez-Curtis
authors.forename: Neeta
authors.initials: N
authors.lastname: Shirvaikar
authors.forename: A Robert
authors.initials: AR
authors.lastname: Turner
authors.forename: Imran
authors.initials: I
authors.lastname: Mirza
authors.forename: Amir
authors.initials: A
authors.lastname: Surmawala
authors.forename: Loree M
authors.initials: LM
authors.lastname: Larratt
authors.forename: Anna
authors.initials: A
authors.lastname: Janowska-Wieczorek