Identification of novel tumor markers for oral squamous cell carcinoma using glycoproteomic analysis
Identification of novel tumor markers for oral squamous cell carcinoma using glycoproteomic analysis
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DOI：
10.1016/j.cca.2012.10.019
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发表时间：
2013-05-01
影响因子：
5
通讯作者：
Chang, Chuan-Fa
中科院分区：
文献类型：
--
作者：
Chen, Yi-Ting;Chong, Yi-Min;Chang, Chuan-Fa
背景：口腔癌是头颈癌中最大的亚型，在过去二十年中已成为最致命的恶性肿瘤之一。虽然一些诊断工具已经应用于口腔恶性肿瘤的早期检测，但仍然迫切需要识别新的肿瘤标志物。在这项研究中，我们探讨了原代培养的人口腔角质形成细胞（HOK）、永生化的人牙龈角质形成细胞（SG细胞）和口腔鳞状细胞癌（OC2）的细胞表面n -糖苷。方法：采用MALDI-TOF质谱法对酶解细胞表面n -聚糖进行分析。结果：OC2细胞表面可见高水平的聚焦型n -聚糖，特别是核心聚焦型n -聚糖，而SG和HOK细胞表面的主要n -聚糖为高甘露糖型。OC2细胞中focusyltransferase 8 mRNA表达水平明显高于SG和HOK细胞。然后用凝集素亲和层析纯化OC2细胞的核心聚焦糖蛋白，并鉴定出癌细胞中的关键粘附分子CD147。最后，在OC2细胞和口腔癌组织（组织阵列）上证实了细胞表面CD147的过表达。结论：CD147是通过糖蛋白组学方法发现的，有望成为口腔癌诊断的新型肿瘤标志物。(c) 2012 Elsevier B.V.版权所有
Background: Oral cancer, the largest subset of head and neck cancer, has become one of the most lethal malignancies during the last two decades. Although several diagnostic tools have been applied for the early detection of oral malignancies, it is still urgent to identify novel tumor markers. In this study, we explored the cell surface N-glycomes of primary cultured human oral keratinocytes (HOK), immortalized human gingival keratinocytes (SG cells), and oral squamous cell carcinoma (OC2).Methods: Enzymatically hydrolyzed cell surface N-glycans were analyzed by MALDI-TOF mass spectrometry.Results: High levels of fucosylated N-glycans, especially core-fucosylated N-glycans, were observed on the OC2 cell surface whereas the major N-glycans on SG and HOK cells were high mannose type. In addition, the mRNA expression level of fucosyltransferase 8 was elevated significantly in OC2 cells than in SG and HOK cells. Core-fucosylated glycoproteins of OC2 cells were then purified with lectin affinity chromatography and a key adhesion molecule in cancer cells, CD147, was identified. Finally, overexpression of cell surface CD147 was confirmed on OC2 cells and oral cancer tissues (tissue array).Conclusions: CD147 was discovered by glycoproteomic approaches and suggested to be a potential novel tumor marker for oral cancer diagnosis. (c) 2012 Elsevier B.V. All rights reserved.