Guangzhou First Municipal People's Hospital, Affiliated Guangzhou Medical College, Guangzhou, China.
J Surg Res. 2010 May 15;160(2):260-7. doi: 10.1016/j.jss.2008.11.838. Epub 2008 Dec 10.
CD147/extracellular matrix metalloproteinase inducer (EMMPRIN) expressed by tumor cells stimulates peri-tumorous fibroblasts to produce matrix metalloproteinases (MMPs), thus contributing to tumor invasion and metastasis. To assess its suitability as a potential therapeutic target, as well as its association with the clinicopathologic features and the prognosis of patients, the expression of CD147/EMMPRIN in neoplastic tissues of the genitourinary system were analyzed.
CD147/EMMPRIN expression in 52 patients with renal carcinoma, 58 patients with bladder carcinoma, 101 patients with prostate carcinoma, 17 patients of penis carcinoma, and 17 patients of testis carcinoma were examined by immunostaining on paraffin-embedded tumor specimens using monoclonal antibodies. Then, the association of its expression with clinicopathologic characteristics to the patients' prognosis was analyzed. The RNA interference approach was used to silence CD147/EMMPRIN expression in the human prostate carcinoma cell line LNCAP and human bladder carcinoma cell line J82. The in vitro proliferative ability of CD147/EMMPRIN-deficient cells was determined by a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide MTT assay.
CD147/EMMPRIN was expressed in neoplastic tissues, but not in normal tissues. Positive expression was shown in 42 of 52 (80.77%) of the patients with renal carcinoma, 41 of 58 (70.69%) of the patients with bladder carcinoma, 67 of 101 (66.34%) of the patients with prostate carcinoma, 16 of 17 (94.12%) of the patients with penis carcinoma and testis carcinoma. Positive CD147/EMMPRIN staining was significantly associated with TNM stages and histological subtypes of patients with various urinary carcinomas (P < 0.05). In all five groups, for different expression levels of CD147/EMMPRIN, the patients with a highly positive expression of CD147/EMMPRIN had the poorest prognosis. The siRNA-treated cells exhibited significantly decreased growth ability compared with control cells in vitro.
These results may assist in defining the suitability of CD147/EMMPRIN as a therapeutic target and as a method for predicting a poor outcome in patients with various urinary carcinomas.
肿瘤细胞表达的 CD147/细胞外基质金属蛋白酶诱导因子(EMMPRIN)可刺激肿瘤周围成纤维细胞产生基质金属蛋白酶(MMPs),从而促进肿瘤侵袭和转移。为了评估其作为潜在治疗靶点的适宜性及其与患者临床病理特征和预后的关系,分析了泌尿系统肿瘤组织中 CD147/EMMPRIN 的表达。
采用免疫组化法,用单克隆抗体对 52 例肾癌、58 例膀胱癌、101 例前列腺癌、17 例阴茎癌和 17 例睾丸癌患者的石蜡包埋肿瘤标本进行 CD147/EMMPRIN 表达检测。然后,分析其表达与临床病理特征对患者预后的关系。采用 RNA 干扰技术沉默人前列腺癌细胞系 LNCAP 和人膀胱癌细胞系 J82 中的 CD147/EMMPRIN 表达。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐 MTT 法测定 CD147/EMMPRIN 缺陷细胞的体外增殖能力。
CD147/EMMPRIN 在肿瘤组织中表达,而在正常组织中不表达。42 例肾癌(80.77%)、41 例膀胱癌(70.69%)、67 例前列腺癌(66.34%)、16 例阴茎癌和睾丸癌患者的肿瘤组织呈阳性表达。CD147/EMMPRIN 阳性染色与不同尿路上皮癌患者的 TNM 分期和组织学亚型显著相关(P<0.05)。在所有五组中,对于 CD147/EMMPRIN 的不同表达水平,CD147/EMMPRIN 高表达的患者预后最差。与对照组相比,siRNA 处理的细胞在体外的生长能力明显下降。
这些结果可能有助于确定 CD147/EMMPRIN 作为治疗靶点和预测各种尿路上皮癌患者预后不良的方法的适宜性。