Expression of Toll-like Receptor 4 is Down-regulated During Progression of Cervical Neoplasia

Overview

Journal Cancer Immunol Immunother

Specialties Allergy & Immunology
Oncology
Pharmacology

Date 2010 Feb 24

PMID 20177675

Citations 31

Authors

Li Yu

Liantang Wang

Mengzhen Li

Juemin Zhong

Zhuo Wang

Shangwu Chen

Affiliations

Soon will be listed here.

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 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.

Citing Articles

TLR4 Downregulation Identifies High-Risk HPV Infection and Integration in H-SIL and Squamous Cell Carcinomas of the Uterine Cervix.

Santoro A, Angelico G, Arciuolo D, Scaglione G, Urtueta B, Aquino G Curr Issues Mol Biol. 2024; 46(10):11282-11295.

PMID: 39451550 PMC: 11506170. DOI: 10.3390/cimb46100670.

Subgroup Analysis of TLR2, -3, -4 and -8 in Relation to the Severity of Clinical Manifestations of Cervical HPV Infection.

Dushkin A, Afanasiev M, Afanasiev S, Grishacheva T, Biryukova E, Dushkina I Int J Mol Sci. 2024; 25(17).

PMID: 39273663 PMC: 11395980. DOI: 10.3390/ijms25179719.

Inhibition of TLR7 and TLR9 Reduces Human Cholangiocarcinoma Cell Proliferation and Tumor Development.

Mohamed F, Jalan R, Minogue S, Andreola F, Habtesion A, Hall A Dig Dis Sci. 2021; 67(5):1806-1821.

PMID: 33939146 DOI: 10.1007/s10620-021-06973-9.

The prognostic role of tissue TLR2 and TLR4 in colorectal cancer.

Beilmann-Lehtonen I, Bockelman C, Mustonen H, Koskensalo S, Hagstrom J, Haglund C Virchows Arch. 2020; 477(5):705-715.

PMID: 32424768 PMC: 7581516. DOI: 10.1007/s00428-020-02833-5.

HPV-mediated down-regulation of NOD1 inhibits apoptosis in cervical cancer.

Liu X, Ma H, Fei L, Jiang M, Xia M, Bai L Infect Agent Cancer. 2020; 15:6.

PMID: 32021648 PMC: 6993450. DOI: 10.1186/s13027-020-0272-3.

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