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 A. Marquez, Akinobu Matsuzaki, Haroon R. Hashmi, Lori M. Larratt, Lynn M. Boshkov, A. Robert Turner, Melissa C. Zhang, Dylan R. Edwards, Anna E. Kossakowska

Research output: Contribution to journalArticlepeer-review

94 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)402-411
Number of pages10
JournalBritish Journal of Haematology
Volume105
Issue number2
DOIs
StatePublished - 1999

Keywords

  • Acute myelogenous leukaemia
  • MMP-2
  • MMP-9
  • TIMP-1
  • TIMP-2

ASJC Scopus subject areas

  • Hematology

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