Altered redox status accompanies progression to metastatic human bladder cancer.
Altered redox status accompanies progression to metastatic human bladder cancer.
复制标题
氧化还原状态的改变伴随着人类转移性膀胱癌的进展。
DOI：
10.1016/j.freeradbiomed.2008.09.020
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发表时间：
2009-01-01
影响因子：
7.4
通讯作者：
Melendez, J. Andres
中科院分区：
文献类型：
--
作者：
Hempel, Nadine;Ye, Hanqing;Abessi, Bryan;Mian, Badar;Melendez, J. Andres
活性氧（ROS）在膀胱癌进展中的作用仍然是一个未探索的领域。调节活性氧水平的酶的表达水平在癌症中经常发生改变。公开的微阵列数据显示，线粒体锰超氧化物歧化酶（Sod2）的表达在高级别和晚期膀胱肿瘤中持续增加，Sod2负责将超氧化物（O2-）转化为过氧化氢（H2O2）。在这里，我们的目的是确定Sod2表达和ROS在膀胱癌中的作用。利用体外人膀胱肿瘤模型，我们监测了非转移性（253J）和高度转移性（253J B-V）膀胱肿瘤细胞系的氧化还原状态。253J B-V细胞与亲本253J细胞系相比，Sod2蛋白和活性水平显著提高。Sod2表达量的增加伴随着过氧化氢酶活性的显著降低，导致253J B-V系H2O2产量的净增加。在转移细胞系中，促转移因子和促血管生成因子、基质金属蛋白酶9 （MMP-9）和血管内皮源性生长因子（VEGF）的表达也同样上调。MMP-9和VEGF的表达都是H2O2依赖性的，因为过氧化氢酶的过表达会减弱它们的表达。同样，过氧化氢酶的表达有效地降低了253J B-V细胞的克隆活性。这些发现表明，转移性膀胱癌细胞显示出抗氧化表达谱的改变，导致ROS产生的净增加，从而导致氧化还原敏感的促肿瘤和促转移基因如VEGF和MMP-9的诱导。
The role of reactive oxygen species (ROS) in bladder cancer progression remains an unexplored field. Expression levels of enzymes regulating ROS levels are often altered in cancer. Search of publicly available micro-array data reveals that expression of mitochondrial manganese superoxide dismutase (Sod2), responsible for the conversion of superoxide (O2-.) to hydrogen peroxide (H2O2), is consistently increased in high grade and advanced stage bladder tumors. Here we aim to identify the role of Sod2 expression and ROS in bladder cancer. Using an in vitro human bladder tumor model we monitored the redox state of both non-metastatic (253J) and highly metastatic (253J B-V) bladder tumor cell lines. 253J B-V cells displayed significantly higher Sod2 protein and activity levels compared to their parental 253J cell line. The increase in Sod2 expression was accompanied by a significant decrease in catalase activity, resulting in a net increase in H2O2 production in the 253J B-V line. Expression of pro-metastatic and –angiogenic factors, matrix metalloproteinase 9 (MMP-9) and vascular endothelial derived growth factor (VEGF), respectively, were similarly upregulated in the metastatic line. Expression of both MMP-9 and VEGF were shown to be H2O2-dependent, as removal of H2O2 by overexpression of catalase attenuated their expression. Similarly, expression of catalase effectively reduced the clonogenic activity of 253J B-V cells. These findings indicate that metastatic bladder cancer cells display an altered antioxidant expression profile, resulting in a net increase in ROS production, which leads to the induction of redox-sensitive pro-tumorigenic and pro-metastatic genes such as VEGF and MMP-9.
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影响因子：
56.9
作者：
AMES, BN
通讯作者：
AMES, BN
影响因子：
6.6
作者：
DINNEY, CPN;FISHBECK, R;KILLION, JJ
通讯作者：
KILLION, JJ
影响因子：
4
作者：
Lewis, A;Du, J;Cullen, JJ
通讯作者：
Cullen, JJ
影响因子：
4.8
作者：
Connor, KM;Subbaram, S;Melendez, JA
通讯作者：
Melendez, JA
影响因子：
11.2
作者：
Connor, Kip M.;Hempel, Nadine;Melendez, J. Andres
通讯作者：
Melendez, J. Andres