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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.
AuthorsLeah A Marquez-Curtis, Neeta Shirvaikar, A Robert Turner, Imran Mirza, Amir Surmawala, Loree M Larratt, Anna Janowska-Wieczorek
JournalCancers (Cancers (Basel)) Vol. 4 Issue 3 Pg. 743-62 (Jul 25 2012) ISSN: 2072-6694 [Print] Switzerland
PMID24213464 (Publication Type: Journal Article)

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