Expression profile of hydrogen sulfide and its synthases correlates with tumor stage and grade in urothelial cell carcinoma of bladder
Expression profile of hydrogen sulfide and its synthases correlates with tumor stage and grade in urothelial cell carcinoma of bladder
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DOI：
10.1016/j.urolonc.2015.06.020
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发表时间：
2016-04-01
影响因子：
2.7
通讯作者：
Ma, Hong-Shun
中科院分区：
文献类型：
--
作者：
Gai, Jun-Wei;Qin, Wei;Ma, Hong-Shun
研究背景：硫化氢（H2S）是一种新发现的气体传递物质。由胱硫醚β-合酶（CBS）、胱硫醚γ-裂解酶（CSE）和3-巯基丙酮酸硫转移酶（MPST）合成。内源性硫化氢从未在膀胱癌中研究过。目的：我们评估了人膀胱移行细胞癌（膀胱尿路上皮细胞癌[UCB]）组织和细胞系中H2S的产生及其H2S酶的表达水平。材料和方法：对94例不同分期/分级的UCB患者的尿路上皮细胞系和膀胱标本进行免疫组化染色。通过图像半定量分析、蛋白质印迹和硫敏电极分析标本和细胞系的CBS、CSE和MPST的表达水平/活性。我们试图找出硫化氢及其代谢酶与脐带血肿瘤分期的相关性。结果：CBS、CSE和MPST在所有被检组织和培养细胞的尿路上皮和肌层中均呈阳性反应。CBS、CSE和MPST的表达水平与UCB分期/分级相关。肌肉浸润性膀胱癌样品显示出最高的H2S产生（52.6 +/- 2.91 nmol/[mg . min]），而EJ细胞（移行细胞癌，III级）在所有测试的细胞系中显示出最高的H2S产生（53.3 +/- 7.02 nmol/[mg .结论：CBS、CSE和MPST在人膀胱组织和人UCB细胞系中的蛋白水平和催化活性随着恶性程度的增加而增加。我们的研究结果可能会促进这些新的酶的应用，UCB的诊断或治疗。(C)2016 Elsevier Inc. All rights reserved.
Background: Hydrogen sulfide (H2S) is a newly discovered gas transmitter. It is synthesized by cystathionine beta-synthase (CBS), cystathionine gamma-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (MPST). Endogenous hydrogen sulfide has never been studied in bladder cancer.Purpose: We evaluated H2S production and its synthases expression levels in transitional cell carcinoma (urothelial cell carcinoma of bladder [UCB]) of human bladder tissue and cell lines.Materials and methods: Immunostaining was performed in urothelial cell lines and bladder specimens from 94 patients with UCB of different stages/grades. The expression levels/activities of CBS, CSE, and MPST of specimens and cell lines were analyzed by image semiquantity assay, western blot, and a sulfur-sensitive electrode. We tried to find the correlation between hydrogen sulfide and its synthases with tumor stage in UCB. All experiments were repeated at least 3 times.Results: Immunoreactivity for CBS, CSE, and MPST was detected in malignant uroepithelium and muscular layer of all tissues examined and cultured cells. The expression levels of CBS, CSE, and MPST were associated with UCB stage/grade. Muscle-invasive bladder cancer samples showed the highest production of H2S (52.6 +/- 2.91 nmol/[mg . min]) among all tested samples and EJ cells (transitional cell carcinoma, grade IIIshowed the highest production of H2S among all tested cell lines (53.3 +/- 7.02 nmol/[mg . mini).Conclusions: Protein levels and catalytic activities of CBS, CSE, and MPST increased with the increase of malignant degrees in human bladder tissues and human UCB cell lines. Our findings may promote the application of these novel enzymes to UCB diagnosis or treatment. (C) 2016 Elsevier Inc. All rights reserved.