High incidence of EMMPRIN expression in human tumors
High incidence of EMMPRIN expression in human tumors
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DOI：
10.1002/ijc.22062
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发表时间：
2006-10-15
影响因子：
6.4
通讯作者：
Pantel, Klaus
中科院分区：
文献类型：
--
作者：
Riethdorf, Sabine;Reimers, Natalie;Pantel, Klaus
肿瘤细胞表达的细胞外基质金属蛋白酶诱导因子刺激瘤周成纤维细胞产生基质金属蛋白酶，从而促进肿瘤的侵袭和转移。为了评估其作为潜在治疗靶点的适用性，分析了正常和肿瘤组织中EMMPRIN表达的总体发生率。使用单克隆抗体MEM-M6/1和HIM 6和组织微阵列分别检测了来自129种不同肿瘤类型和76种不同正常组织的2，348和608个组织样本的EMMPRIN表达。用识别不同糖结构的单克隆抗体和生物化学方法通过Western印迹分析分析人乳腺癌细胞中EMMPRIN的表达和糖基化状态。在分析的129个肿瘤实体中，有112个实体存在EMMPRIN表达，恶性肿瘤的EMMPRIN阳性率高于良性肿瘤。EMMPRIN表达在肿瘤实体之间存在显著异质性。其中，鳞状细胞癌（60-100%）、胰腺癌（87%）、嫌色性肾癌（83%）、肝细胞癌（83%）或髓样乳腺癌（83%）腺癌以及多形性胶质母细胞瘤（79%）的EMMPRIN表达率特别高。EMMPRIN阳性的正常细胞类型数量有限，包括增殖活性和分化的上皮细胞、生殖细胞、左心室的心肌细胞或脑的血管内皮细胞。我们可以进一步证明，乳腺癌细胞表达的EMMPRIN亚型在存在或不存在刘易斯（X）聚糖结构方面存在差异。我们的研究结果可能有助于确定EMMPRIN作为治疗靶点的适用性和预测不良副作用。(c)2006 Wiley-Liss，Inc.
Extracellular matrix metalloproteinase inducer expressed by tumor cells stimulates peritumoral fibroblasts to produce matrix metalloproteinases, thus contributing to tumor invasion and metastasis. To assess its suitability as potential therapeutic target, the overall incidence of EMMPRIN expression in normal and neoplastic tissues was analyzed. EMMPRIN expression was detected immunohistochemically using monoclonal antibodies MEM-M6/1 and HIM6 and tissue microarrays with 2,348 and 608 tissue samples from 129 distinct tumor types and 76 different normal tissues, respectively. Expression and glycosylation state of EMMPRIN in human breast cancer cells were analyzed by Western blot analysis with monoclonal antibodies recognizing distinct carbohydrate structures and biochemical methods. EMMPRIN expression was found in 112 of 129 tumor entities analyzed with malignant tumors being EMMPRIN positive more frequently than benign tumors. A remarkable heterogeneity in EMMPRIN expression between tumor entities was observed. Among others, squamous-cell carcinomas (60-100%), pancreatic (87%), chromophobic kidney (83%), hepatocellular (83%) or medullary breast (83%) adenocarcinomas as well as glioblastoma multiforme (79%) presented with a particular high incidence of EMMPRIN expression. There were a limited number of EMMPRIN-positive normal cell types including proliferatively active and differentiating epithelial cells, germ cells, myocardial cells in the left heart ventricle or vascular endothelial cells of the brain. We could further demonstrate that breast cancer cells expressed EMMPRIN isoforms differing in the presence or absence of Lewis(X) glycan structures. Our results may assist in defining the suitability of EMMPRIN as therapeutic target and predicting negative side effects. (c) 2006 Wiley-Liss, Inc.