Department of Pathology, The First Affiliated Hospital, Sun Yat-sen (Zhongshan) University, Guangzhou, People's Republic of China.
Cancer Immunol Immunother. 2010 Jul;59(7):1021-8. doi: 10.1007/s00262-010-0825-1. Epub 2010 Feb 23.
Chronic infection and inflammation are among the most important factors contributing to cancer development and growth. Toll-like receptors (TLRs) are important families of pattern recognition receptors, which recognize conserved components of microbes and trigger the immune response against invading microorganisms. TLR4 is the signaling receptor for lipopolysaccharide (LPS), the endotoxic component of Gram-negative bacteria. Recent studies demonstrate that TLRs are expressed in some tumor cells, and that the expression of TLRs in these cells is associated with tumorigenesis. Cervical intraepithelial neoplasia (CIN) is a key stage in the development of cervical cancer and human papillomavirus (HPV) infection is an essential factor in cervical carcinogenesis. As the cervix is in constant contact with bacteria, especially Gram-negative bacteria, we hypothesize that TLR4-mediated bacterial stimulation may be involved in the tumorigenesis of cervical cancer. In the present study, the expression and distribution of TLR4 in CIN and cervical squamous carcinoma were investigated by immunohistochemistry. To our surprise, we observed a decrease in the expression of TLR4 during the progression of cervical neoplasia and this down-regulation of TLR4 appeared to be associated with the expression of P(16INK4A) which is a crucial marker of HPV integration into host cells. These data offer further insight regarding the association of HPV infection and TLR signaling during the carcinogenesis of cervical cancer.
慢性感染和炎症是导致癌症发展和生长的最重要因素之一。Toll 样受体（TLRs）是模式识别受体的重要家族，可识别微生物的保守成分，并引发针对入侵微生物的免疫反应。TLR4 是脂多糖（LPS）的信号受体，LPS 是革兰氏阴性菌的内毒素成分。最近的研究表明，TLRs 在一些肿瘤细胞中表达，并且这些细胞中 TLRs 的表达与肿瘤发生有关。宫颈上皮内瘤变（CIN）是宫颈癌发展的关键阶段，人乳头瘤病毒（HPV）感染是宫颈癌发生的重要因素。由于宫颈与细菌（尤其是革兰氏阴性菌）不断接触，我们假设 TLR4 介导的细菌刺激可能参与宫颈癌的肿瘤发生。在本研究中，通过免疫组织化学研究了 TLR4 在 CIN 和宫颈鳞癌中的表达和分布。令我们惊讶的是，我们观察到在宫颈肿瘤发生过程中 TLR4 的表达下降，这种 TLR4 的下调似乎与 P(16INK4A)的表达有关，P(16INK4A)是 HPV 整合到宿主细胞中的关键标志物。这些数据进一步深入了解了 HPV 感染和 TLR 信号在宫颈癌致癌过程中的关联。
