Department of Obstetrics and Gynecology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
BMC Cancer. 2012 May 28;12:191. doi: 10.1186/1471-2407-12-191.
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.
细胞外基质金属蛋白酶诱导因子（Emmprin/CD147）是一种跨膜糖蛋白，属于免疫球蛋白超家族。Emmprin 在许多肿瘤细胞表面丰富，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。
通过免疫组织化学法检测正常子宫内膜、子宫内膜增生和癌症标本中 Emmprin 的表达。此外，还在 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 的表达水平显著升高（p<0.05）。高 Emmprin 表达的患者无病生存率（DFS）和总生存率（OS）显著高于低 Emmprin 表达的患者（DFS：p<0.001；OS：p<0.001）。siRNA 介导的 Emmprin 敲低通过 TGF-β、EGF、NF-κB、VEGF、MMP-2 和 MMP-9 的表达导致细胞增殖、迁移和侵袭，进而导致子宫内膜癌中 E-钙黏蛋白水平升高，波形蛋白和 Snail 水平降低。
本研究结果表明，低 Emmprin 表达可能是子宫内膜癌患者预后良好的预测指标，Emmprin 可能是子宫内膜癌的潜在治疗靶点。
