Expression And Functional Research Of TLR4 In Human Cervical Carcinoma

Cervical cancer is one of the most common gynecological malignancies, accounts for about 12% of all cancers in women, and seriously affect the health of women. The researches in recent years show that cervical cancer is an inflammatory disease. HPV persistent infection was the main pathogenic factors of cervical cancer. HPV viral oncogenes can integrate into the DNA of host cervical basal layer cells and cause the cervical epithelial cells undergo malignant transformation. Recently, the relation between the development of carcinoma and inflammation are increasingly linked and the role of inflammation in carcinogenesis again brought people's attention. Through many kinds of complex mechanisms, such as antiapoptotic function of the nuclear transcription factors (NF-kB), the induction of DNA oxidative damage and the repair response of injury and so on, Chronic infections may regulate the development of carcinoma. The growth of Cancer can cause tissue injury and some anomalous changes of microenvironment, further stimulate inflammation and induce secretion of inflammatory mediators, angiogenesis and remodeling of tissues. However, what the key trigger components of inflammation involved in carcinogensis are not clear. TLRs is the most characteristic pathogen pattern recognition receptors, play an important role in defense of infections. Emerging evidence suggests that TLRs are expressed not only on immune cells but also on many cancer cells. Chronic inflammation mediated by TLRs may not only act on host cells and directly involve in the initiation and development of cancer, but also shape regulation tumor microenvironment to influence carcinogenesis. However, what is the biological function of TLRs on tumor cells remains to be thoroughly understood. Furthermore, studies on the expression of TLRs in cervical cancer are limited. Current pertinent efforts are mainly focused on TLR5 and TLR9.As an important transmembrane pattern recognition receptor, TLR4 can not only recognizes exogenous ligand lipopolysaccharide (LPS), but also endogenous ligands. TLR4 can regulate the inflammation response and shape the tumor microenvironment by recognetion the endogenous and exogenous ligands.The cervix is frequently exposed to the endogenous vaginal bacterial flora environment, which exists large TLRs ligand, especially TLR4, rather than HPV environment. Most reproductive females may suffer from HPV infection in their life, and most of them can regress after lasting for six to 12 months. Immune tolerance and escape may be the key reasons to HPV persistent infection. Theoretically, TLRs by signaling pathways mediated inflammation of host, shape the body's immune environment, secrete a lot of proinflammation factors, such as interferons, to regulate virus infection. Current researches about the relations between HPV and TLRs are limited. The specific mechanisms are unclear. Therefore, we firstly selected TLR4 to explore whether it would involve in the initiation or development of cervical carcinoma and discuss the correlation with HPV infection.