TY - JOUR
T1 - Expression of matrix metalloproteinases (MMP-2 and -9) and tissue inhibitors of metalloproteinases (TIMP-1 and -2) in acute myelogenous leukaemia blasts
T2 - Comparison with normal bone marrow cells
AU - Janowska-Wieczorek, Anna
AU - Marquez, Leah A.
AU - Matsuzaki, Akinobu
AU - Hashmi, Haroon R.
AU - Larratt, Lori M.
AU - Boshkov, Lynn M.
AU - Turner, A. Robert
AU - Zhang, Melissa C.
AU - Edwards, Dylan R.
AU - Kossakowska, Anna E.
PY - 1999
Y1 - 1999
N2 - 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.
AB - 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.
KW - Acute myelogenous leukaemia
KW - MMP-2
KW - MMP-9
KW - TIMP-1
KW - TIMP-2
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UR - http://www.scopus.com/inward/citedby.url?scp=0032898121&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2141.1999.01352.x
DO - 10.1111/j.1365-2141.1999.01352.x
M3 - Article
C2 - 10233411
AN - SCOPUS:0032898121
SN - 0007-1048
VL - 105
SP - 402
EP - 411
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 2
ER -