Department of Gynecology; The First Affiliated Hospital of China Medical University; Shenyang, China.
Cell Cycle. 2013 Sep 1;12(17):2899-913. doi: 10.4161/cc.25950. Epub 2013 Aug 8.
Extracellular matrix metalloproteinase inducer (EMMPRIN) was reported to involve in the invasion and metastasis of malignancies by regulating the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) in stromal and cancer cells. The study aimed to clarify the role of EMMPRIN expression in tumorigenesis and progression of ovarian epithelial carcinomas.
EMMPRIN siRNA were transfected into ovarian carcinoma cells with the phenotypes and their related molecules examined. EMMPRIN expression was determined in ovarian normal tissue, benign and borderline tumors, and epithelial carcinomas by real-time PCR, western blot, and immunohistochemistry.
EMMPRIN siRNA treatment resulted in a lower growth, G 1 arrest, apoptotic induction, decreased migration, and invasion. The transfectants showed reduced expression of Wnt5a, Akt, p70s6k, Bcl-xL, survivin, VEGF, and MMP-9 than mock and control cells at both mRNA and protein levels. According to real-time PCR and western blot, EMMPRIN mRNA or protein level was higher in ovarian borderline tumor and carcinoma than normal ovary and benign tumors (P<0.05), and positively correlated with dedifferentiation and FIGO staging (P<0.05). Immunohistochemically, EMMPRIN expression was positively correlated with FIGO staging, dedifferentiation, Ki-67 expression, the lower cumulative and relapse-free survival rate (P<0.05).
Upregulated expression of EMMPRIN protein and mRNA might be involved in the pathogenesis, differentiation, and progression of ovarian carcinomas, possibly by modulating cellular events, such as proliferation, cell cycle, apoptosis, migration, and invasion.
细胞外基质金属蛋白酶诱导因子（EMMPRIN）通过调节基质细胞和癌细胞中血管内皮生长因子（VEGF）和基质金属蛋白酶（MMPs）的表达，被报道参与恶性肿瘤的侵袭和转移。本研究旨在阐明 EMMPRIN 表达在卵巢上皮性癌发生和进展中的作用。
用 EMMPRIN siRNA 转染具有表型的卵巢癌细胞，并检测相关分子。采用实时 PCR、western blot 和免疫组化法检测卵巢正常组织、良性和交界性肿瘤以及上皮性癌中 EMMPRIN 的表达。
EMMPRIN siRNA 处理导致生长减慢、G1 期阻滞、凋亡诱导、迁移和侵袭减少。转染细胞在 mRNA 和蛋白水平上显示出 Wnt5a、Akt、p70s6k、Bcl-xL、存活素、VEGF 和 MMP-9 的表达低于 mock 和对照细胞。根据实时 PCR 和 western blot，卵巢交界性肿瘤和癌组织中 EMMPRIN mRNA 或蛋白水平高于正常卵巢和良性肿瘤（P<0.05），且与去分化和 FIGO 分期呈正相关（P<0.05）。免疫组化结果显示，EMMPRIN 表达与 FIGO 分期、去分化、Ki-67 表达、累积和无复发生存率降低呈正相关（P<0.05）。
EMMPRIN 蛋白和 mRNA 的上调表达可能参与了卵巢癌的发病机制、分化和进展，可能通过调节细胞增殖、细胞周期、凋亡、迁移和侵袭等细胞事件。
