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Expression and Functional Analysis of Toll-like Receptor 4 in Human Cervical Carcinoma

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Abstract

Toll-like receptors are expressed in human immune cells and many tumors, but the role of toll-like receptor 4 (TLR4) in the development of tumors is controversial. We demonstrated the expression, distribution, and functional activity of TLR4 in tissues of normal cervix, cervical intraepithelial neoplasia (CIN), invasion cervical cancers (ICC), and different human papillomavirus (HPV)-infected cervical cancer cells. The results showed that TLR4 expression was in accordance with the histopathological grade: higher in ICC than in CIN, and low in normal cervical tissues and malignant cervical stroma. Expression was higher in SiHa (HPV16+) than in HeLa (HPV18+) cells, but was not observed in C33A (HPV−) cells. After treatment with its agonist, lipopolysaccharide (LPS), the expression levels of TLR4 was increased and apoptosis resistance was induced in SiHa cells, but not in HeLa or C33A cells. Meanwhile, LPS treatment did not alter the cell cycle distribution in SiHa cells. The mechanism of apoptosis resistance may be related to HPV16 infection and not correlated with the cell cycle distribution. Targeting TLR4 in combination with traditional drug treatment may serve as a novel strategy for more effectively killing cancer cells.

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Acknowledgments

We thank Prof. Weidong Yao in the Department of Pathology, Yantai YuHuangDing Hospital, QingDao University of Medicine for providing us with pathological samples and technical advice. This work was supported by Grants from the National Natural Science Foundation of China (No. 81101971), Guangdong Natural Science Foundation (No. B2011295, No. S2011040006012), and the “973” Program of China (Grant 2009CB521800).

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The authors have no conflicting financial interests.

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Authors and Affiliations

  1. Gynecological Minimal Invasive Center, Beijing Obstetrics Gynecology Hospital, Capital Medical University, Beijing, 100006, China

    Yongjun Wang & Hua Duan

  2. Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China

    Yanjie Weng, Ying Shi & Shixuan Wang

  3. Department of Gynecology & Obstetrics, Affiliated Shenzhen Nanshan Hospital, Guangdong Medical College, Shenzhen, 518052, Guangdong, People’s Republic China

    Xi Xia

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  1. Yongjun Wang
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Correspondence to Yanjie Weng.

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Wang, Y., Weng, Y., Shi, Y. et al. Expression and Functional Analysis of Toll-like Receptor 4 in Human Cervical Carcinoma. J Membrane Biol 247, 591–599 (2014). https://doi.org/10.1007/s00232-014-9675-7

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