Extracellular redox state regulates features associated with prostate cancer cell invasion
Extracellular redox state regulates features associated with prostate cancer cell invasion
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DOI：
10.1158/0008-5472.can-08-0162
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发表时间：
2008-07-15
期刊：
影响因子：
11.2
通讯作者：
Oberley, Terry D.
中科院分区：
文献类型：
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作者：
Chaiswing, Luksana;Zhong, Weixiong;Oberley, Terry D.
我们研究了细胞外还原-氧化（氧化还原）状态在调节与前列腺癌细胞侵袭相关的生物/生化特征中的可能作用。采用DU145、PC-3和rwpe1来源的人前列腺癌（WPE1-NB26）细胞系进行体外分析。使用s -亚硝基-n -乙酰青霉胺增加一氧化氮水平导致细胞入侵能力下降，而使用黄嘌呤/黄嘌呤氧化酶增加细胞外超氧化物自由基（O-2（中心点-））水平导致细胞入侵能力增加。与RWPE1细胞（永生化但非恶性前列腺上皮细胞）相比，WPE1-NB26细胞在培养基中表现出谷胱甘肽/谷胱甘肽二硫比增加，表明WPE1-NB26细胞的细胞外氧化还原状态发生了改变。我们假设O-2（中心点-）在质膜或邻近细胞外基质处或附近的产生至少部分调节前列腺癌细胞的侵袭。利用腺病毒介导的细胞外超氧化物歧化酶（EC- SOD）基因转导降低O-2（中心点-）水平，我们发现在肝素存在的情况下，腺病毒EC-SOD基因转导导致细胞外EC-SOD表达增加，从而抑制细胞侵袭能力。这种抑制与金属蛋白酶[基质金属蛋白酶（MMP） 2/膜型1-MMP]活性降低和细胞外亚硝酸盐水平升高相关。我们的研究结果表明，细胞外氧化还原状态在细胞侵袭调节中的突出作用，这可能为治疗干预提供机会。
We have examined the possible role of extracellular reduction-oxidation (redox) state in regulation of biological/biochemical features associated with prostate cancer cell invasion. DU145, PC-3, and RWPE1-derived human prostate cancer (WPE1-NB26) cell lines were used for the present in vitro analysis. Increasing levels of nitric oxide using S-nitroso-N-acetylpenicillamine resulted in a decrease in cell invasion ability, whereas increasing levels of extracellular superoxide radical (O-2(center dot-)) using xanthine/xanthine oxidase resulted in an increase in cell invasion ability in these three cell lines. WPE1-NB26 cells exhibited an increased glutathione/glutathione disulfide ratio in the medium in comparison with RWPE1 cells (immortalized but nonmalignant prostate epithelial cells), suggesting an alteration of extracellular redox state of WPE1-NB26 cells. We hypothesized that O-2(center dot-) production at or near the plasma membrane or in the adjacent extracellular matrix at least partially regulated prostate cancer cell invasion. Using adenovirus-mediated extracellular superoxide dismutase (EC- SOD) gene transduction to enzymatically decrease O-2(center dot-) levels, we showed that in the presence of heparin, adenovirus EC- SOD gene transduction resulted in an increase in the expression of EC-SOD outside the cells with resultant inhibition of cell invasion ability. This inhibition correlated with reduced metalloproteinase [matrix metalloproteinase (MMP) 2/membrane type 1-MMP] activities and increased levels of extracellular nitrite. Our results suggest a prominent role of extracellular redox status in regulation of cell invasion, which may provide opportunities for therapeutic interventions.