Department of Gynecology, Women's Hospital, School of Medicine, Zhejiang University, 1Xueshi Road, Hangzhou 310006, P.R. China.
Department of Gynecology, Women's Hospital, School of Medicine, Zhejiang University, 1Xueshi Road, Hangzhou 310006, P.R. China.
Toxicol Lett. 2018 Jun 15;290:19-28. doi: 10.1016/j.toxlet.2018.03.009. Epub 2018 Mar 10.
Polychlorinated biphenyls (PCBs), as part of environmental contaminants, have been proved to be related to endometriosis. This study is to investigate the effect of PCB 104 on cell migration, invasion and resultant gene expression in endometrial stromal cells (ESCs). Fifty-three specimens of eutopic endometrial tissues were collected from twenty-four women with endometriosis (EU-EMS) and twenty-nine women without endometriosis (EU-NON). Both EU-EMS and EU-NON were divided into the PCB 104 exposure group and the control group according to whether they were exposed to PCB 104. Primary cultured ESCs were exposed to PCB 104 at the micro molar doses (2 × 10, 0.2 and 1 μmol/L) and concentrations of 2, 5 and 10 μmol/L in six-well plates. Cell mobility and proliferation assay were used to evaluate the effects of PCB 104 on the migration, invasion and proliferation of ESCs, and the effect of PCB 104 on actin cytoskeleton was also examined by immunofluorescence. Subsequently, the mRNA levels of related genes including matrix metalloproteinase (MMP) -2, -3, -9, -10, E-cadherin, Snail, Slug and tissue inhibitor of metalloproteinase (TIMP) -2 in ESCs were examined by using real-time PCR, as well as protein levels of MMP-3 and MMP-10 were detected by enzyme-linked immunosorbent assay (ELISA). We explored the role of epidermal growth factor receptor (EGFR) in the expression of MMP-3 and MMP-10 induced by PCB 104. Exposure to PCB 104 significantly increased the migration and invasion of ESCs. The mRNA and protein levels of MMP-3 and MMP-10 in ESCs treated with PCB 104 were higher than that in the control, with a dose- and time-dependent manner in mRNA level, while the expression of MMP-2, MMP-9, TIMP-2, E-cadherin, Snail and Slug did not change significantly. Taken together, PCB 104 promotes migration and invasion of ESCs by inducing the expression of MMP-3 and MMP-10, which may involved the EGFR signalling pathway.
多氯联苯(PCBs)作为环境污染物的一部分,已被证明与子宫内膜异位症有关。本研究旨在探讨 PCB 104 对子宫内膜基质细胞(ESCs)迁移、侵袭和相关基因表达的影响。从 24 名子宫内膜异位症患者(EU-EMS)和 29 名无子宫内膜异位症患者(EU-NON)中采集了 53 份在位子宫内膜组织标本。根据是否接触 PCB 104,将 EU-EMS 和 EU-NON 分为 PCB 104 暴露组和对照组。在六孔板中,将原代培养的 ESCs 暴露于微摩尔剂量(2×10、0.2 和 1μmol/L)和浓度为 2、5 和 10μmol/L 的 PCB 104 中。细胞迁移和增殖试验用于评估 PCB 104 对 ESCs 迁移、侵袭和增殖的影响,并用免疫荧光法检测 PCB 104 对肌动蛋白细胞骨架的影响。随后,通过实时 PCR 检测 ESCs 中基质金属蛋白酶(MMP)-2、-3、-9、-10、E-钙黏蛋白、Snail、Slug 和金属蛋白酶组织抑制剂(TIMP)-2 等相关基因的 mRNA 水平,并用酶联免疫吸附试验(ELISA)检测 MMP-3 和 MMP-10 的蛋白水平。我们探讨了表皮生长因子受体(EGFR)在 PCB 104 诱导的 MMP-3 和 MMP-10 表达中的作用。接触 PCB 104 可显著增加 ESCs 的迁移和侵袭。与对照组相比,用 PCB 104 处理的 ESCs 中 MMP-3 和 MMP-10 的 mRNA 和蛋白水平均升高,且呈剂量和时间依赖性,而 MMP-2、MMP-9、TIMP-2、E-钙黏蛋白、Snail 和 Slug 的表达无明显变化。综上所述,PCB 104 通过诱导 MMP-3 和 MMP-10 的表达促进 ESCs 的迁移和侵袭,这可能涉及 EGFR 信号通路。