Expression of cancer stem cell marker during 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis
Expression of cancer stem cell marker during 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis
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DOI：
10.1007/s10735-014-9584-1
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发表时间：
2014-12-01
影响因子：
3.2
通讯作者：
Kim, Okjoon
中科院分区：
文献类型：
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作者：
Lim, Wonbong;Choi, Hongran;Kim, Okjoon
关于口腔癌发生的理论之一是，肿瘤生长是从癌症干细胞（CSC）开始的，这些干细胞自我更新并产生分化的肿瘤细胞，就像正常组织中的干细胞一样。CSC鉴定的最常见方法是基于癌发生过程中CSC标志物的表达。本研究检测了口腔鳞状细胞肉瘤（SCC）中最常用的CSC生物标志物CD 133和CD 44的表达，目的是确定其表达与多步骤口腔癌发生相关的分子生物标志物。采用免疫组化和Western blot方法检测4-硝基喹啉1-氧化物诱导的大鼠舌癌模型中CD 133、CD 44、增殖细胞核抗原（PCNA）和细胞角蛋白（CK）的表达。此外，通过蛋白质印迹研究了醛脱氢酶1（ALDH 1）、OCT-4和Nanog的表达对癌细胞干细胞性的改变。沿着多步癌变过程，异型增生组CD 133、CD 44表达较正常组略有增加。而CD 133蛋白在SCC中呈高表达。PCNA和CK在正常组中呈低表达，而在SCC中表达逐渐增高。ALDH 1、Nanog和OCT-4的表达随SCC分级的升高而升高。研究结果表明，CD 133在识别口腔CSC中是有用的，这表明CD 133可以作为识别具有口腔癌发展高风险的CSC的预测因子。
One of the theories regarding oral carcinogenesis is that the tumor growth is initiated from cancer stem cells (CSCs) that self-renew and give rise to differentiated tumor cells, like stem cells do in normal tissues. The most common methods of CSC identification are based on CSC marker expression in carcinogenesis. This study examined the expression of CD133 and CD44, the most commonly used CSC biomarkers in oral squamous cell sarcoma (SCC), with the goal of identifying molecular biomarkers whose expression is associated with the multistep oral carcinogenesis. The expression of CD133, CD44, proliferating cell nuclear antigen (PCNA), and Cytokeratin (CK) was examined by Western blot analysis and confirmed by immunohistochemistry in a 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis model. Also, the expression of aldehyde dehydrogenase 1 (ALDH1), OCT-4 and Nanog were investigated for alteration of cancer cell stemness by Western blot. Along with the progress of multistep carcinogenesis, there were slight increases of CD133 and CD44 expression in the dysplasia group compared with normal rats. However, CD133 protein level was significantly overexpressed in SCC. The expression of PCNA and CK were low in normal group, but sequentially increased in SCC. ALDH1, Nanog and OCT-4 expression were significantly increased according to SCC grade during carcinogenesis. The findings indicate that CD133 is useful in identifying oral CSCs, which suggests that CD133 may serve as a predictor to identify CSCs with a high risk of oral cancer development.