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Expression of toll-like receptor 4 is down-regulated during progression of cervical neoplasia

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Abstract

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 \( {\text{P}}^{{ 1 6^{\text{INK4A}} }} , \) 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.

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Acknowledgments

We are most grateful to Dr. Jacob Couturier, Department of internal medicine, University of Texas-Health Science Center at Houston (Houston, TX, USA), for language review. This study was funded by the Ph.D. Program Foundation of Ministry of Education of China (20090171110029) and grants from Yuexiu Science and Technology Bureau of Guangzhou, China (2005-WS-001, 2008-WS-003).

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Authors and Affiliations

  1. Department of Pathology, The First Affiliated Hospital, Sun Yat-sen (Zhongshan) University, Guangzhou, 510080, People’s Republic of China

    Li Yu, Liantang Wang, Juemin Zhong & Zhuo Wang

  2. State Key Laboratory for Biocontrol, Guangdong Key Laboratory of Pharmaceutical Functional Genes, Department of Biochemistry, School of Life Sciences, Sun Yat-sen (Zhongshan) University, Guangzhou, 510275, People’s Republic of China

    Mengzhen Li & Shangwu Chen

  3. Department of Pathology, The Yuexiu Hospital of Guangzhou, Guangzhou, People’s Republic of China

    Li Yu

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  1. Li Yu
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Correspondence to Li Yu or Shangwu Chen.

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Yu, L., Wang, L., Li, M. et al. Expression of toll-like receptor 4 is down-regulated during progression of cervical neoplasia. Cancer Immunol Immunother 59, 1021–1028 (2010). https://doi.org/10.1007/s00262-010-0825-1

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  • DOI: https://doi.org/10.1007/s00262-010-0825-1

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