TLR4及其在卵巢癌细胞增殖调控中的研究进展

Progress of Toll-like receptor4 and its regulation in the proliferation of ovary carcinoma cells

Toll样受体-4(TLR4)可识别病原相关分子模式(PAMP),是脂多糖的唯一功能性受体,其不仅发挥抗感染免疫作用,也参与调控肿瘤细胞的增殖与存活。X射线晶体学显示,脂多糖等刺激机体细胞后,TLR4与MD2发生异二聚体化,形成MD2/TLR4受体复合物,TLR4胞内域发生活化,并募集Myd88等相关接头蛋白,激活下游NF-κB等信号通路,发挥抗感染免疫作用。TLR4除了正常的生殖道上皮组织中可见表达外,卵巢上皮性肿瘤、颗粒细胞瘤及其细胞株也可见差异表达,并参与卵巢上皮性肿瘤及卵巢颗粒细胞瘤的异常增殖调控,揭示TLR4介导的慢性炎症可能参与卵巢肿瘤的发生发展。

Toll-like receptor 4 （TLR4） is an important family of pattern recognition receptors. It can recognize pathogen associated molecular patterns and trigger protective responses to the invading pathogens, which mainly express in immune cells and constitute a major part of the innate immune system. The current evidences demonstrate the impact of TLR4 in abnormal proliferation and survival. Recently, x-ray crystallography presents formation of MD2/TLR4 complex through activation of bacterial endotoxin in these cells. Functional TLR4 results in recruitment of adaptor protein include Myd88 and activation of transduetion signal such as NF-κB. In the current review, we focused on the progress of TLR4 and its role in ovary carcinoma. Besides the role in some epithelial cells, TLR4 has been detected in many tumor cell lines or tumors, especially epithelial-derived ovary cancers. Nevertheless, its role in human ovarian granulosa tumor cells has also been discovered, which shows the relationship between inflammation and cancer.