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

被引:68
作者
Janowska-Wieczorek, A
Marquez, LA
Matsuzaki, A
Hashmi, HR
Larratt, LM
Boshkov, LM
Turner, AR
Zhang, MC
Edwards, DR
机构
[1] Univ Alberta, Dept Med, Canadian Blood Serv, Edmonton Ctr, Edmonton, AB T6G 2R8, Canada
[2] Univ Calgary, Dept Pathol, Calgary, AB, Canada
[3] Univ E Anglia, Dept Sci Biol, Norwich NR4 7TJ, Norfolk, England
关键词
MMP-2; MMP-9; TIMP-1; TIMP-2; acute myelogenous leukaemia;
D O I
10.1046/j.1365-2141.1999.01352.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:402 / 411
页数:10
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