Membrane Type-1 Matrix Metalloproteinase Expression in Acute Myeloid Leukemia and Its Upregulation by Tumor Necrosis Factor-α
| Autor: | Amir Surmawala, Neeta Shirvaikar, Anna Janowska-Wieczorek, Loree Larratt, Leah A. Marquez-Curtis, A. Robert Turner, Imran Mirza |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Cancer Research
Stromal cell macromolecular substances Matrix metalloproteinase acute myeloid leukemia matrix metalloproteinase-2 lcsh:RC254-282 Article 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation stomatognathic system hemic and lymphatic diseases Medicine Gene silencing 030304 developmental biology membrane type 1-matrix metalloproteinase 0303 health sciences business.industry Activator (genetics) Myeloid leukemia lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens 3. Good health Haematopoiesis Oncology 030220 oncology & carcinogenesis Immunology embryonic structures Cancer research Tumor necrosis factor alpha tumor necrosis factor-α business |
| Zdroj: | Cancers Volume 4 Issue 3 Pages 743-762 Cancers, Vol 4, Iss 3, Pp 743-762 (2012) |
| ISSN: | 2072-6694 |
| DOI: | 10.3390/cancers4030743 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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