Tumour-like phenotypes in urothelial cells after exposure to antigens from eggs of Schistosoma haematobium: An oestrogen-DNA adducts mediated pathway?
Tumour-like phenotypes in urothelial cells after exposure to antigens from eggs of Schistosoma haematobium: An oestrogen-DNA adducts mediated pathway?
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DOI：
10.1016/j.ijpara.2012.10.023
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发表时间：
2013-01-01
影响因子：
4
通讯作者：
Correia da Costa, Jose Manuel
中科院分区：
文献类型：
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作者：
Botelho, Monica C.;Vale, Nuno;Correia da Costa, Jose Manuel
血吸虫、埃及血吸虫的慢性感染与膀胱鳞状细胞癌有关。此前，研究表明，混合性成虫埃及沙门氏菌 (SWAP) 的可溶性提取物在体外和体内均具有致瘤性。此外，埃及沙门氏菌 SWAP 中的雌激素相关分子下调雌激素反应细胞中的雌激素受体 (ER) α 和 β。此外，血吸虫病患者的血清中存在血吸虫雌激素，并抑制尿路上皮细胞中 ER 的转录。鉴于埃及沙门氏菌卵是直接导致血吸虫病期间泌尿生殖系统疾病的发育阶段，我们怀疑埃及沙门氏菌卵的可溶性抗原表现出类似或更强大的致瘤能力。在这里，我们研究了埃及沙门氏菌可溶性卵抗原（Sh-SEA）的致瘤潜力以及有利于血吸虫寄生的内分泌系统。研究结果证实，6.25μg/ml的Sh-SEA足以刺激细胞增殖、减少细胞凋亡并增加暴露于Sh-SEA的尿路上皮细胞的氧化应激。此外，通过使用碱性单细胞凝胶电泳（Comet）测定了Sh-SEA对这些细胞的基因毒性作用。此外，液相色谱二极管阵列检测电子喷雾电离质谱表明 S. haematobium SEA 中存在儿茶酚雌激素。还讨论了埃及沙门氏菌卵诱导的膀胱癌中潜在的雌激素-DNA 加合物介导的途径。 (C) 2012 年澳大利亚寄生虫学协会。由 Elsevier Ltd 出版。保留所有权利。
Chronic infection with the blood fluke, Schistosoma haematobium, is associated with squamous cell carcinoma of the bladder. Previously, it has been shown that soluble extracts of mixed sex adult S. haematobium worms (SWAP) are tumourigenic, both in vitro and in vivo. In addition, oestrogen-related molecules in SWAP of S. haematobium down-regulate oestrogen receptors (ERs) alpha and beta in oestrogen responsive cells. Moreover, schistosome oestrogens occur in sera of persons with schistosomiasis haematobia and repress transcription of ERs in urothelial cells. Given that eggs of S. haematobium are the developmental stage directly responsible for urogenital disease during schistosomiasis haematobia, we suspected that soluble antigens from S. haematobium eggs exhibit similar or more potent tumorigenic capacity. Here we investigated the tumorigenic potential of soluble egg antigens (Sh-SEA) of S. haematobium and the endocrine system in favouring parasitism by schistosomes. The findings confirmed that 6.25 mu g/ml of Sh-SEA was enough to stimulate cell proliferation, reduce apoptosis and increase oxidative stress of Sh-SEA-exposed urothelial cells. In addition, genotoxic effects of Sh-SEA on these cells were determined by using alkaline single-cell gel electrophoresis (Comet). Furthermore, Liquid Chromatography Diode Array Detection Electron Spray Ionisation Mass Spectrometry indicated the presence of catechol-oestrogens in S. haematobium SEA. A prospective oestrogen-DNA adduct mediated pathway in S. haematobium egg induced bladder cancer is also discussed. (C) 2012 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.