Northern Ontario School of Medicine, Lakehead University, Thunder Bay, Ontario, Canada.
Innate Immun. 2012 Feb;18(1):55-69. doi: 10.1177/1753425910392934. Epub 2011 Jan 14.
We hypothesized that development of cervical cancer is associated with alterations in the expression of innate immune receptors, i.e. integrins and TLRs, and that these alterations can be induced by infectious agents. We have studied the expression of these proteins in cervical biopsy tissues and cervical cancer-derived cell lines HeLa, CaSki, SiHa, C-33 A, and ME180. Immunohistochemistry analysis demonstrated an increase in integrin αv, β3, β4, and β6 expression in the epithelium during the development of cervical cancer. A clear trend towards higher expression of integrin β6 in cell lines harbouring human papillomavirus (HPV) genetic material, compared to HPV-negative C-33 A, was observed. To investigate whether bacterial infection can alter the expression of TLRs and integrins, we infected HeLa cells by two pathogens, Escherichia coli and Pseudomonas aeruginosa, using a common bacterium of the female genital tract, Lactobacillus reuteri, as a control. Infection with E. coli or P. aeruginosa, but not with L. reuteri, significantly altered the expression of TLR and integrins, particularly of TLR4 and integrin β6. Considering that both integrin β6 and TLR4 play important roles in tumorigenesis, our data suggest that bacterial infection may trigger cancer development in HPV-infected cervical epithelium.
我们假设宫颈癌的发生与固有免疫受体（即整合素和 TLR）的表达改变有关，并且这些改变可以由感染因子诱导。我们研究了这些蛋白质在宫颈活检组织和宫颈癌衍生的细胞系 HeLa、CaSki、SiHa、C-33A 和 ME180 中的表达。免疫组织化学分析表明，在宫颈癌的发展过程中，上皮细胞中整合素 αv、β3、β4 和 β6 的表达增加。与 HPV 阴性的 C-33A 相比，HPV 遗传物质存在的细胞系中整合素 β6 的表达明显更高，呈现出一种清晰的趋势。为了研究细菌感染是否可以改变 TLR 和整合素的表达，我们用两种病原体大肠杆菌和铜绿假单胞菌感染了 HeLa 细胞，并用女性生殖道常见细菌罗伊氏乳杆菌作为对照。大肠杆菌或铜绿假单胞菌感染，但不是罗伊氏乳杆菌感染，显著改变了 TLR 和整合素的表达，特别是 TLR4 和整合素 β6。鉴于整合素 β6 和 TLR4 都在肿瘤发生中发挥重要作用，我们的数据表明细菌感染可能会引发 HPV 感染的宫颈上皮的癌症发展。
