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
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
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DOI：
10.1046/j.1365-2141.1999.01352.x
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发表时间：
1999-05-01
影响因子：
6.5
通讯作者：
Edwards, DR
中科院分区：
文献类型：
--
作者：
Janowska-Wieczorek, A;Marquez, LA;Edwards, DR
我们比较了基质金属蛋白酶的表达（MMP-2和MMP-9）和金属蛋白酶的组织抑制剂（TIMP-1和TIMP-2）在骨髓急性髓性白血病（AML）原始细胞和白血病细胞系中的作用（HEL、HL-60、K-562和KG-1）与它们在正常骨髓细胞中的表达进行比较。所有测试的AML样品和白血病细胞系表达MMP-9和/或MMP-2 mRNA，因此这些明胶酶分泌到培养基中。此外，TIMP-1和TIMP-2的mRNA和分泌蛋白在所有AML样品中被证实。尽管所有白血病细胞系均表达TIMP-1，但HL-60细胞也表达TIMP-2。正常骨髓未成熟祖细胞（CD 34（+）细胞）不表达或分泌MMP-2和MMP-9，但正常骨髓中更多的成熟单核细胞表达和分泌MMP-9。正常骨髓CD 34（+）细胞和单核细胞表达TIMP-1和TIMP-2 mRNA，但这些蛋白用反向酶谱法检测不到。此外，而骨髓成纤维细胞和内皮细胞分泌的只有潜在的MMP-2，这种酶的激活形式被发现在培养基中的细胞从长期培养的正常和AML骨髓粘附层的条件。我们发现白血病细胞明胶酶、TIMP-1和TIMP-2的表达上调，提示这些蛋白质可能与AML的侵袭性表型有关。
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.