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探索异尖线虫寄生虫的致瘤潜力:一项初步研究。

Exploring tumourigenic potential of the parasite Anisakis: a pilot study.

作者信息

Corcuera María Teresa, Rodríguez-Bobada Cruz, Zuloaga Jaime, Gómez-Aguado Fernando, Rodríguez-Perez Rosa, Mendizabal Ángel, González Pablo, Arias-Díaz Javier, Caballero María Luisa

机构信息

Department of Microbiology, La Paz University Hospital, Madrid, Spain.

Experimental Medicine and Department of Surgery, Hospital Clínico San Carlos, Madrid, Spain.

出版信息

Parasitol Res. 2018 Oct;117(10):3127-3136. doi: 10.1007/s00436-018-6008-2. Epub 2018 Jul 13.

Abstract

Anisakiasis is a global disease caused by consumption of raw or lightly cooked fish parasitised with Anisakis spp. third-stage larvae. Cases in the literature show colocalised anisakiasis and colorectal cancer, and the incidental finding of Anisakis larvae at the tumour site was reported. Data from our group suggested an epidemiological link between previous infection and gastrointestinal cancer. Furthermore, it has recently been reported that Anisakis products lead to inflammation and DNA damage. Based on these facts, the aim was to investigate whether Anisakis antigens are able to induce changes in the proliferation of epithelial cells in vitro or in the expression of serum microRNA (miRNA) in Sprague-Dawley rats. Anisakis complete extract (CE) induced increases in cell proliferation and decreases in apoptosis compared with nontreated cells, which resulted in a significant increase in the absolute number of viable cells at 48 h of exposure (P < .05). Furthermore, the miRNAs mmu-miR-1b-5p and mmu-miR-10b-5p (a cancer-related miRNA) were significantly decreased (P < .05) in sera from the rats inoculated with Anisakis CE, compared with control rats inoculated with saline. Additionally, based on their relative quantification values, four other cancer-related miRNAs were considered to be differently expressed, rno-miR-218a-5p and mmu-miR-224-5p (decreased) and rno-miR-125a-3p and rno-miR-200c-3p (increased). Anisakis CE was able to induce changes both in epithelial cells in vitro and in an animal model. The results obtained with Anisakis CE, in terms of increasing cell proliferation, decreasing apoptosis and inducing changes in the expression of serum cancer-related miRNAs in rats, suggest that Anisakis could have tumourigenic potential.

摘要

异尖线虫病是一种全球性疾病,由食用寄生有异尖线虫属三期幼虫的生鱼或轻度烹饪的鱼引起。文献中的病例显示异尖线虫病与结直肠癌共定位,并且有报道称在肿瘤部位偶然发现了异尖线虫幼虫。我们团队的数据表明既往感染与胃肠道癌之间存在流行病学联系。此外,最近有报道称异尖线虫产物会导致炎症和DNA损伤。基于这些事实,本研究旨在探讨异尖线虫抗原是否能够在体外诱导上皮细胞增殖变化或在Sprague-Dawley大鼠血清微小RNA(miRNA)表达方面产生变化。与未处理的细胞相比,异尖线虫全提取物(CE)可诱导细胞增殖增加和凋亡减少,这导致暴露48小时时活细胞绝对数量显著增加(P < 0.05)。此外,与接种生理盐水的对照大鼠相比,接种异尖线虫CE的大鼠血清中miRNAs mmu-miR-1b-5p和mmu-miR-10b-5p(一种与癌症相关的miRNA)显著降低(P < 0.05)。此外,根据它们的相对定量值,另外四种与癌症相关的miRNAs被认为表达存在差异,rno-miR-218a-5p和mmu-miR-224-5p(降低)以及rno-miR-125a-3p和rno-miR-200c-3p(升高)。异尖线虫CE能够在体外上皮细胞以及动物模型中诱导变化。就增加细胞增殖、减少凋亡以及诱导大鼠血清中与癌症相关的miRNAs表达变化而言,异尖线虫CE所获得的结果表明异尖线虫可能具有致瘤潜力。

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