Stimulation of matrix metalloproteinase-9 expression in human fibrosarcoma cells by synthetic matrix metalloproteinase inhibitors.
Stimulation of matrix metalloproteinase-9 expression in human fibrosarcoma cells by synthetic matrix metalloproteinase inhibitors.
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合成基质金属蛋白酶抑制剂刺激人纤维肉瘤细胞中基质金属蛋白酶 9 的表达。
DOI：
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发表时间：
2002
影响因子：
3.7
通讯作者：
J. Foidart
中科院分区：
文献类型：
--
作者：
E. Maquoi;C. Munaut;A. Colige;C. Lambert;F. Frankenne;A. Noël;F. Grams;H. Krell;J. Foidart
基质金属蛋白酶-2(MMP2)和MMP9的高表达和激活与肿瘤的进展、侵袭和转移密切相关。使用合成的基质金属蛋白酶抑制剂来阻断这些酶的蛋白分解活性，最近出现了一种潜在的治疗癌症的工具。在这项研究中，我们报道了合成的广谱基质金属蛋白酶抑制剂GI129471通过基底膜的主要成分IV型胶原有效地降低了HT1080细胞的体外侵袭力。这种侵袭力的降低与完全抑制原-基质金属蛋白酶-2的激活是平行的；然而，GI129471强烈增加了分泌的原-基质金属蛋白酶-9的数量，随后可以通过纤溶酶原依赖的机制激活。定量RT-PCR和Northern印迹分析表明，GI129471特异性地增加了基质金属蛋白酶-9mRNA的稳态水平。此外，瞬时将含有不同长度的基质金属蛋白酶-9基因5‘侧翼区的β-半乳糖苷酶报告载体导入HT1080细胞，发现相应启动子的转录活性上调。已知的基质金属蛋白酶-9的表达调节物，如IL-1β和肿瘤坏死因子-α，并不参与这种上调。这些发现强调了基质金属蛋白酶表达调控的复杂性，以及需要详细描述与使用广谱MMPI相关的潜在副作用。
Enhanced expression and activation of matrix metalloproteinase-2 (MMP-2) and MMP-9 have been associated with tumor progression, invasion, and metastasis. The use of synthetic MMP inhibitors to block the proteolytic activity of these enzymes recently emerged as a potential therapeutic tool to treat cancer. In this study, we report that GI129471, a synthetic broad-spectrum MMP inhibitor, efficiently reduced the in vitro invasiveness of HT1080 cells through type IV collagen, a major component of basement membranes. This reduced invasion was paralleled by a complete inhibition of pro-MMP-2 activation; however, GI129471 strongly increased the amount of secreted pro-MMP-9, which could be subsequently activated through a plasminogen-dependent mechanism. Quantitative RT-PCR and northern blot analysis revealed that GI129471 specifically increased the MMP-9 mRNA steady-state level. Moreover, transient transfection of HT1080 cells with beta-galactosidase reporter vectors containing different lengths of the 5'-flanking region of the MMP-9 gene revealed an upregulation of the transcriptional activity of the corresponding promoter. Well-known modulators of MMP-9 expression such as Il-1beta and TNF-alpha were not involved in this upregulation. These findings emphasize the complexity of the regulation of MMP expression and the requirement for a detailed characterization of the potential adverse side effects associated with the use of broad-spectrum MMPIs.
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DOI：
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发表时间：
1993-07
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
A. Strongin;B. Marmer;G. A. Grant;G. Goldberg
通讯作者：
A. Strongin;B. Marmer;G. A. Grant;G. Goldberg
影响因子：
11.2
作者：
Jin Hua;R. Muschel
通讯作者：
Jin Hua;R. Muschel
影响因子：
11.2
作者：
Y. DeClerck;T. Yean;D. Chan;Hiroyuki Shimada;K. Langley
通讯作者：
Y. DeClerck;T. Yean;D. Chan;Hiroyuki Shimada;K. Langley
微管中 GTP 水解伴随的结构变化：来自缓慢水解类似物鸟苷基-(α,β)-亚甲基二膦酸酯的信息。
DOI：
10.1083/jcb.128.1.117
发表时间：
1995-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hyman AA;Chrétien D;Arnal I;Wade RH
通讯作者：
Wade RH
IL-10 通过“侵袭刺激因子”激活的 PC-3 ML 细胞阻断 IV 型胶原蛋白侵袭：上调 TIMP-1 表达。
DOI：
--
发表时间：
1995
期刊：
Oncology research.
影响因子：
--
作者：
Stearns,ME;Wang,M;Stearns,M
通讯作者：
Stearns,M