Role of emmprin in endometrial cancer.
Role of emmprin in endometrial cancer.
复制标题
DOI：
10.1186/1471-2407-12-191
复制
发表时间：
2012-05-28
期刊：
影响因子：
3.8
通讯作者：
Hiramatsu Y
中科院分区：
文献类型：
--
作者：
Nakamura K;Kodama J;Hongo A;Hiramatsu Y
细胞外基质金属蛋白酶诱导剂 (Emmprin/CD147) 是一种属于免疫球蛋白超家族的跨膜糖蛋白。 emmprin富集在许多肿瘤细胞的表面，促进肿瘤生长、侵袭、转移和血管生成。我们评估了 emmprin 的临床重要性并研究了其在子宫内膜癌中的作用。通过免疫组织化学方法检测子宫正常子宫内膜、增生子宫内膜和癌症标本中 Emmprin 的表达。此外，在 HEC-50B 和 KLE 子宫内膜癌细胞系中研究了 emmprin 敲低的生物学功能和抑制作用。与正常子宫内膜和子宫内膜增生标本相比，子宫内膜癌标本中emmprin表达水平显着升高（p<0.05）。 emmprin高表达患者的无病生存率（DFS）和总生存率（OS）显着高于emmprin低表达患者（DFS：p< 0.001；OS：p< 0.001）。 siRNA 敲低 Emmprin，通过 TGF-β、EGF、NF-κB、VEGF、MMP-2 和 MMP-9 表达导致细胞增殖、迁移和侵袭，进而导致子宫内膜癌中 E-钙粘蛋白水平升高，波形蛋白和 Snail 水平降低。目前的研究结果表明，低 emmprin 表达可能是子宫内膜癌患者良好预后的预测因子，并且 emmprin 可能代表子宫内膜癌的潜在治疗靶点。
Extracellular matrix metalloproteinase inducer (Emmprin/CD147) is a transmembrane glycoprotein that belongs to the immunoglobulin superfamily. Enriched on the surface of many tumor cells, emmprin promotes tumor growth, invasion, metastasis and angiogenesis. We evaluated the clinical importance of emmprin and investigated its role in endometrial cancer. Emmprin expression was examined in uterine normal endometrium, endometrial hyperplasia and cancer specimens by immunohistochemistry. In addition, the biological functions and inhibitory effects of an emmprin knockdown were investigated in HEC-50B and KLE endometrial cancer cell lines. The levels of emmprin expression were significantly increased in the endometrial cancer specimens compared with the normal endometrium and endometrial hyperplasia specimens (p < 0.05). The disease-free survival (DFS) and overall survival (OS) rates of patients with high emmprin expression were significantly higher than those of patients with low emmprin expression (DFS: p < 0.001; OS: p < 0.001). Emmprin knockdown by the siRNA led to cell proliferation, migration and invasion through TGF-β, EGF, NF-κB, VEGF, MMP-2, and MMP-9 expression, which in turn resulted in increased levels of E-cadherin and reduced levels of Vimentin and Snail in endometrial cancer. The present findings suggest that low emmprin expression might be a predictor of favorable prognosis in endometrial cancer patients, and that emmprin may represent a potential therapeutic target for endometrial cancer.