颗粒蛋白前体诱导上皮间质转化促进上皮性卵巢癌细胞侵袭和迁移的研究

Study on the cell invasion and migration of epithelial ovary cancer promoted by epithelial- mesenchymal transition induced by progranulin

目的研究颗粒蛋白前体(PGRN)在上皮性卵巢癌(EOC)中的表达差异及其促进EOC发展的分子机制。方法搜集2008年1月到2011年12月在山东大学齐鲁医院就诊的良性上皮性卵巢肿瘤、上皮性卵巢癌患者肿瘤组织的石蜡切片,采用免疫组织化学染色的方法检测PGRN在良性卵巢上皮性肿瘤、EOC中的表达差异;采用Transwell小室方法检测PGRN对EOC细胞侵袭、迁移能力的影响;运用Western Blot法探讨PGRN促进肿瘤细胞侵袭、迁移的分子机制。结果 PGRN在良性上皮性卵巢肿瘤组免疫组化评分:(3.2941±1.0317)分,在EOC组免疫组化评分:(8.5500±0.7014)分(P<0.001)。在EOC组中PGRN的表达与Snail的表达呈正相关(P<0.01)。Transwell结果显示在SK-OV-3细胞中敲低PGRN后,穿至小室膜下层的细胞数比对照组明显减少(P<0.05)。Western Blot结果显示在SK-OV-3细胞中敲低PGRN后,E-cadherin、ZO-1表达显著增强,N-cadherin、Vimentin、Snail、p-AKT、p-mT OR表达明显降低(P<0.05)。结论 PGRN可能通过激活Akt/mT OR/Snail信号通路诱导EOC细胞发生上皮间质转化(EMT),进而促进肿瘤细胞的侵袭、迁移。

Objective To discuss the different expression of progranulin（PGRN） between benign ovarian epithelial tumors and epithelial ovarian cancers, and to explore the molecular mechanisms of PGRN in promoting development of epithelial ovarian cancer. Methods We collected the paraffin sections of benign epithelial ovarian tumor and epithelial ovarian cancer（EOC） in Shandong University Qilu Hospital from January 2008 to December 2011. The immunohistochemical staining was used to detect the different expression of PGRN between two groups. Transwell Chambers was used to detect the migration and invasiveness ability of EOC cells; Western blotting was used to study the molecular mechanism of PGRN in promoting the invasion and migration of tumor cells. Results PGRN is over-expressed in epithelial ovarian cancer（3.2941±1.0317 vs. 8.5500±0.7014, P0.001）. There is a positive correlation between PGRN and Snail expression in epithelial ovarian cancer group. PGRN promotes epithelial cancer cell invasion（P〈0.01） and migration（P〈0.05）. The expression of E-cadherin and ZO-1 was increased by knockdown of PGRN, but the expression of Ncadherin,Vimentin,Snail,p-AKT and p-m TOR was reduced（P〈0.05）. Conclusion PGRN is over-expressed in epithelial ovarian cancer. PGRN may induce EMT by activating Akt/m TOR/Snail signaling pathway to promote the invasion and migration of epithelial ovarian cancer cells.