Comprehensive glycomics comparison between colon cancer cell cultures and tumours: Implications for biomarker studies
Comprehensive glycomics comparison between colon cancer cell cultures and tumours: Implications for biomarker studies
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DOI：
10.1016/j.jprot.2014.05.002
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发表时间：
2014-08-28
影响因子：
3.3
通讯作者：
Packer, Nicolle H.
中科院分区：
文献类型：
--
作者：
Chik, Jenny H. L.;Zhou, Jerry;Packer, Nicolle H.
糖基化改变通常在结直肠癌中观察到。体外模型经常用于研究这种癌症，但对这些模型细胞系统和肿瘤组织之间可能存在的差异知之甚少。我们比较了5个结直肠癌细胞系（SW 1116，SW 480，SW 620，SW 837，LS 174 T）的膜蛋白糖基化与上皮细胞从结直肠肿瘤，使用液相色谱串联质谱。值得注意的是，在肿瘤细胞中有五种丰富的O-聚糖，在低粘蛋白产生细胞系中未检测到，尽管在粘液性LS 174 T细胞中发现了两种。O-聚糖包括众所周知的聚糖癌症标志物唾液酸-Tn，其与粘蛋白相关。使用qRT-PCR，发现唾液酸-Tn表达与LS 174 T细胞中α 2，6-唾液酸转移酶基因（ST 6 GALNAC 1）的增加和核心1合酶基因（C1 GALT 1）的减少相关。在LS 174 T细胞中，粘蛋白亚组（MUC 2、MUC 6、MUC 5 B）的表达也与唾液酸-Tn表达相关。总体而言，发现模型细胞系的膜蛋白糖基化彼此不同，并且与肿瘤组织的上皮细胞不同。这些发现应注意的生物标志物发现实验的设计，特别是当细胞表面的目标正在investigated.Biological significanceThe蛋白质糖基化的程度之间的差异在体外细胞系和离体肿瘤在结直肠癌的研究是未知的。我们的研究扩展了目前的知识，通过表征膜蛋白糖基化的五种不同的结直肠癌细胞系和上皮细胞来源于切除的结直肠癌肿瘤组织，使用液相色谱串联质谱。在膜糖蛋白上的N-和O-连接聚糖结构中发现的详细结构差异被确定，并与细胞系中相关蛋白的mRNA表达相关。在培养的癌细胞系和来自肿瘤组织的上皮细胞之间发现的糖基化差异对聚糖生物标志物的发现具有重要意义。皇冠版权所有（C）2014由爱思唯尔B. V.出版保留所有权利。
Altered glycosylation is commonly observed in colorectal cancer. In vitro models are frequently used to study this cancer but little is known about the differences that may exist between these model cell systems and tumour tissue. We have compared the membrane protein glycosylation of five colorectal cancer cell lines (SW1116, SW480, SW620, SW837, LS174T) with epithelial cells from colorectal tumours using liquid chromatography tandem mass spectrometry. Remarkably, there were five abundant O-glycans in the tumour cells that were undetected in the low-mucin producing cell lines, although two were found in the mucinous LS174T cells. The O-glycans included the well-known glycan cancer marker, sialyl-Tn, which has been associated with mucins. Using qRT-PCR, sialyl-Tn expression was found to be associated with an increase in alpha 2,6-sialyltransferase gene (ST6GALNAC1) and a decrease in core 1 synthase gene (C1GALT1) in LS174T cells. The expression of a subset of mucins (MUC2, MUC6, MUC5B) was also correlated with sialyl-Tn expression in LS174T cells. Overall, the membrane protein glycosylation of the model cell lines was found to differ from each other and from the epithelial cells of tumour tissue. These findings should be noted in the design of biomarker discovery experiments particularly when cell surface targets are being investigated.Biological significanceThe extent of protein glycosylation differences between in vitro cell lines and ex vivo tumours in colorectal cancer research is unknown. Our study expands current knowledge by characterising the membrane protein glycosylation profiles of five different colorectal cancer cell lines and of epithelial cells derived from resected colorectal cancer tumour tissue, using liquid chromatography tandem mass spectrometry. The detailed structural differences found in both N- and O-linked glycan structures on the membrane glycoproteins were determined and correlated with the mRNA expression of the relevant proteins in the cell lines. The glycosylation differences found between cultured cancer cell lines and epithelial cells from tumour tissue have important implications for glycan biomarker discovery. Crown Copyright (C) 2014 Published by Elsevier B.V. All rights reserved.