Carcinogenic properties of proteins with pro-inflammatory activity from Streptococcus infantarius (formerly S.bovis)
Carcinogenic properties of proteins with pro-inflammatory activity from Streptococcus infantarius (formerly S.bovis)
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DOI：
10.1093/carcin/bgh091
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发表时间：
2004-08-01
期刊：
影响因子：
4.7
通讯作者：
Schöller-Guinard, M
中科院分区：
文献类型：
--
作者：
Biarc, J;Nguyen, IS;Schöller-Guinard, M
一些研究报告了细菌感染与癌变之间的联系。牛链球菌传统上被认为是低级别病原体，经常涉及菌血症和心内膜炎。这种细菌对人类健康至关重要，因为有研究表明，25-80%出现牛链球菌菌血症的患者同时患有结直肠肿瘤。此外，在之前的实验中，我们证明了S.bovis或S.bovis壁提取抗原（WEA）能够促进大鼠的癌变。本研究的目的是：(i)鉴定负责体外促炎特性的牛链球菌蛋白；（ii）净化；（iii）检测其在体外刺激人结肠癌细胞IL-8和COX-2表达的能力；（iv）在大鼠结肠癌模型中评估其体内促癌潜能。通过蛋白质组学分析，纯化的S300部分在二维凝胶电泳中包含72个蛋白点，代表12种不同的蛋白，能够触发人上皮结肠Caco-2细胞和大鼠结肠粘膜释放CXC趋化因子（人IL-8或大鼠CINC/GRO）和前列腺素E-2，与COX-2在体外过表达相关。此外，这些蛋白在促进氮氧甲烷处理大鼠的肿瘤前病变方面非常有效。在这些蛋白的存在下，Caco-2细胞表现出三种MAP激酶的磷酸化增强。我们的研究结果显示了牛链球菌蛋白的促炎潜能与其促癌特性之间的关系，证实了炎症与结肠癌发生之间的联系。这些数据支持结肠细菌可以促进癌症发展的假设，特别是在慢性感染/炎症疾病中，细菌成分可能干扰细胞功能。
Several studies reported linkage between bacterial infections and carcinogenesis. Streptococcus bovis was traditionally considered as a lower grade pathogen frequently involved in bacteremia and endocarditis. This bacterium became important in human health as it was shown that 25-80% of patients who presented a S.bovis bacteremia had also a colorectal tumor. Moreover, in previous experiments, we demonstrated that S.bovis or S.bovis wall extracted antigens (WEA) were able to promote carcinogenesis in rats. The aim of the present study was: (i) to identify the S.bovis proteins responsible for in vitro pro-inflammatory properties; (ii) to purify them; (iii) to examine their ability to stimulate in vitro IL-8 and COX-2 expression by human colon cancer cells; and (iv) to assess in vivo their pro-carcinogenic potential in a rat model of colon carcinogenesis. The purified S300 fraction, as determined by proteomic analysis, contained 72 protein spots in two-dimensional gel electrophoresis representing 12 different proteins able to trigger human epithelial colonic Caco-2 cells and rat colonic mucosa to release CXC chemokines (human IL-8 or rat CINC/GRO) and prostaglandins E-2, correlated with an in vitro over-expression of COX-2. Moreover, these proteins were highly effective in the promotion of pre-neoplastic lesions in azoxymethane-treated rats. In the presence of these proteins, Caco-2 cells exhibited enhanced phosphorylation of the three classes of MAP kinases. Our results show a relationship between the pro-inflammatory potential of S.bovis proteins and their pro-carcinogenic properties, confirming the linkage between inflammation and colon carcinogenesis. These data support the hypothesis that colonic bacteria can contribute to cancer development particularly in chronic infection/inflammation diseases where bacterial components may interfere with cell function.