Positive correlations of Oct-4 and Nanog in oral cancer stem-like cells and high-grade oral squamous cell carcinoma
Positive correlations of Oct-4 and Nanog in oral cancer stem-like cells and high-grade oral squamous cell carcinoma
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DOI：
10.1158/1078-0432.ccr-07-4404
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发表时间：
2008-07-01
影响因子：
11.5
通讯作者：
Lo, Jeng-Fan
中科院分区：
文献类型：
--
作者：
Chiou, Shih-Hwa;Yu, Cheng-Chia;Lo, Jeng-Fan
目的：口腔鳞状细胞癌（Oral squamous cell carcinoma，OSCC）与许多实体瘤一样，含有异质性的癌细胞群。最近的数据表明，一种罕见的癌细胞亚群，称为癌症干细胞（CSC），能够启动，维持和扩大肿瘤的生长。识别和表征的CSC从OSCC有利于监测，治疗，或预防OSCC.Experimental Design：我们丰富的口腔癌干细胞样细胞（OC-SLC）通过球体形成培养OSCC细胞从建立的OSCC细胞系或原代培养OSCC患者在确定的无血清培养基。阐明了富集OC-SLC和亲代OSCC之间干性基因的差异表达谱。此外，还对口腔鳞癌患者组织中的干细胞标记物进行了免疫组化染色，以评估干细胞基因与口腔鳞癌预后之间的关系。富集的OC-SLC高表达干/祖细胞标志物和ABC转运蛋白基因（Oct-4，Nanog，CD117，Nestin，CD133，和ABCG 2），并且在体外和体内也显示出诱导分化能力和增强的迁移/侵袭/恶性能力。在来自OSCC患者肿瘤的富集的OC-SLC中显示了升高的CD 133表达。Oct-4、Nanog和CD 133的表达与肿瘤分期呈正相关。Kaplan-Meier分析显示Nanog/Oct-4/CD 133三重阳性患者预测OSCC患者的生存预后最差。结论：我们通过球体形成法从OSCC中富集了一个肿瘤干细胞样细胞亚群。富集的OC-SLC具有干细胞和恶性肿瘤的双重特征。此外，干性标志物（Nanog/Oct-4/CD 133）的表达与OSCC患者的生存预后相矛盾。
Purpose: Oral squamous cell carcinoma (OSCC), like many solid tumors, contains a heterogeneous population of cancer cells. Recent data suggest that a rare subpopulation of cancer cells, termed cancer stem cells (CSC), is capable of initiating, maintaining, and expanding the growth of tumor. Identification and characterization of CSC from OSCC facilitates the monitoring, therapy, or prevention of OSCC.Experimental Design: We enriched oral cancer stem-like cells (OC-SLC) through sphere formation by cultivating OSCC cells from established OSCC cell lines or primary cultures of OSCC patients within defined serum-free medium. Differential expression profile of sternness genes between enriched OC-SLC and parental OSCC was elucidated. Furthermore, immunohistochemical staining of sternness markers on OSCC patient tissues was examined to evaluate the association between stemness genes and prognosis of OSCC.Results: Enriched OC-SLC highly expressed the stem/progenitor cell markers and ABC transporter gene (Oct-4, Nanog, CD117, Nestin, CD133, and ABCG2) and also displayed induced differentiation abilities and enhanced migration/invasion/malignancy capabilities in vitro and in vivo. Elevated expression of CD133 was shown in the enriched OC-SLC from OSCC patients' tumors. Positive correlations of Oct-4, Nanog, or CD133 expression on tumor stage were shown on 52 OSCC patient tissues. Kaplan-Meier analyses exhibited that Nanog/Oct-4/CD133 triple-positive patients predicted the worst survival prognosis of OSCC patients.Conclusion: We enriched a subpopulation of cancer stem-like cell from OSCC by sphere formation. The enriched OC-SLC possesses the characteristics of both stem cells and malignant tumors. Additionally, expression of stemness markers (Nanog/Oct-4/CD133) contradicts the survival prognosis of OSCC patients.