Expression of matrix metalloproteinases (MMP-2 and -9) and tissue inhibitors of metalloproteinases (TIMP-1 and -2) in acute myelogenous leukaemia blasts: comparison with normal bone marrow cells
Anna Janowska-Wieczorek,
Leah Marquez,
Akinobu Matsuzaki,
Haroon Hashmi,
Lori Larratt,
Lynn Boshkov,
A. Turner,
Melissa Zhang,
Dylan Edwards,
Anna Kossakowska,
Anna Janowska-Wieczorek
Department of Medicine, University of Alberta, Edmonton,
Search for more papers by this authorLeah Marquez
Department of Medicine, University of Alberta, Edmonton,
Search for more papers by this authorAkinobu Matsuzaki
Department of Medicine, University of Alberta, Edmonton,
Search for more papers by this authorHaroon Hashmi
Department of Medicine, University of Alberta, Edmonton,
Search for more papers by this authorLori Larratt
Department of Medicine, University of Alberta, Edmonton,
Search for more papers by this authorLynn Boshkov
Department of Medicine, University of Alberta, Edmonton,
Search for more papers by this authorA. Turner
Department of Medicine, University of Alberta, Edmonton,
Search for more papers by this authorMelissa Zhang
Department of Pathology, University of Calgary, Alberta, Canada,
Search for more papers by this authorDylan Edwards
Department of Biological Sciences, University of East Anglia, Norwich, U.K.
Search for more papers by this authorAnna Kossakowska
Department of Pathology, University of Calgary, Alberta, Canada,
Search for more papers by this authorAnna Janowska-Wieczorek,
Leah Marquez,
Akinobu Matsuzaki,
Haroon Hashmi,
Lori Larratt,
Lynn Boshkov,
A. Turner,
Melissa Zhang,
Dylan Edwards,
Anna Kossakowska,
Anna Janowska-Wieczorek
Department of Medicine, University of Alberta, Edmonton,
Search for more papers by this authorLeah Marquez
Department of Medicine, University of Alberta, Edmonton,
Search for more papers by this authorAkinobu Matsuzaki
Department of Medicine, University of Alberta, Edmonton,
Search for more papers by this authorHaroon Hashmi
Department of Medicine, University of Alberta, Edmonton,
Search for more papers by this authorLori Larratt
Department of Medicine, University of Alberta, Edmonton,
Search for more papers by this authorLynn Boshkov
Department of Medicine, University of Alberta, Edmonton,
Search for more papers by this authorA. Turner
Department of Medicine, University of Alberta, Edmonton,
Search for more papers by this authorMelissa Zhang
Department of Pathology, University of Calgary, Alberta, Canada,
Search for more papers by this authorDylan Edwards
Department of Biological Sciences, University of East Anglia, Norwich, U.K.
Search for more papers by this authorAnna Kossakowska
Department of Pathology, University of Calgary, Alberta, Canada,
Search for more papers by this authorDr Anna Janowska-Wieczorek Department of Medicine, University of Alberta, Canadian Blood Services, Edmonton Centre, 8249–114 Street, Edmonton, Alberta, Canada T6G 2R8.
Abstract
We compared the expression of matrix metalloproteinases (MMP-2 and MMP-9) and tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) in bone marrow acute myelogenous leukaemia (AML) blasts and leukaemic cell lines (HEL, HL-60, K-562 and KG-1) with their expression in normal bone marrow cells. All AML samples and leukaemic cell lines tested expressed MMP-9 and/or MMP-2 mRNA and, accordingly, these gelatinases were secreted into media. Moreover, TIMP-1 and TIMP-2 mRNA and secreted proteins were demonstrated in all the AML samples. Although all the leukaemic cell lines expressed TIMP-1, the HL-60 cells also expressed TIMP-2. In contrast, normal steady-state bone marrow immature progenitor cells (CD34+ cells) did not express or secrete either MMP-2 or MMP-9, but more mature mononuclear cells from normal bone marrow expressed and secreted MMP-9. Also, normal bone marrow CD34+ cells and mononuclear cells expressed TIMP-1 and TIMP-2 mRNA, but these proteins were not detectable by reverse zymography. Furthermore, whereas bone marrow fibroblasts and endothelial cells secreted only latent MMP-2, the activated form of this enzyme was found in media conditioned by cells obtained from long-term cultures of normal and AML bone marrow adherent layers. Our finding of up-regulated production of gelatinases, TIMP-1 and TIMP-2 by leukaemic cells suggests that these proteins may be implicated in the invasive phenotype of AML.
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