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• Marquez-Curtis, L
• Shirvaikar, N
• Turner, A
• Mirza, I
• Surmawala, A
• Larratt, L
• Janowska-Wieczorek, A
• [+] on Google Scholar
• Marquez-Curtis, L
• Shirvaikar, N
• Turner, A
• Mirza, I
• Surmawala, A
• Larratt, L
• Janowska-Wieczorek, A
• [+] on PubMed
• Marquez-Curtis, L
• Shirvaikar, N
• Turner, A
• Mirza, I
• Surmawala, A
• Larratt, L
• Janowska-Wieczorek, A

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Cancers 2012, 4(3), 743-762; doi:10.3390/cancers4030743

Article

Membrane Type-1 Matrix Metalloproteinase Expression in Acute Myeloid Leukemia and Its Upregulation by Tumor Necrosis Factor-α

Leah A. Marquez-Curtis ¹ , Neeta Shirvaikar ¹ , A. Robert Turner ² , Imran Mirza ³ , Amir Surmawala ² , Loree M. Larratt ²  and Anna Janowska-Wieczorek ^1,2,*

¹ Canadian Blood Services R&D, Edmonton, Alberta T6G 2R8, Canada ² Departments of Medicine and Oncology, University of Alberta, Edmonton, Alberta T6G 2G3, Canada ³ Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta T6G 2B7, Canada

* Author to whom correspondence should be addressed.

Received: 1 June 2012; in revised form: 11 July 2012 / Accepted: 13 July 2012 / Published: 25 July 2012

(This article belongs to the Special Issue Leukemia)

Download PDF Full-Text [359 KB, uploaded 25 July 2012 15:10 CEST]

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.

Keywords: acute myeloid leukemia; membrane type 1-matrix metalloproteinase; matrix metalloproteinase-2; tumor necrosis factor-α

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