中度分化口腔黏膜鳞状细胞癌中癌症干细胞的特征分析
Characterization of Cancer Stem Cells in Moderately Differentiated Buccal Mucosal Squamous Cell Carcinoma.
作者信息
Yu Helen H, Featherston Therese, Tan Swee T, Chibnall Alice M, Brasch Helen D, Davis Paul F, Itinteang Tinte
机构信息
Gillies McIndoe Research Institute , Wellington , New Zealand.
Gillies McIndoe Research Institute, Wellington, New Zealand; Wellington Regional Plastic, Maxillofacial and Burns Unit, Hutt Hospital, Wellington, New Zealand.
出版信息
Front Surg. 2016 Aug 2;3:46. doi: 10.3389/fsurg.2016.00046. eCollection 2016.
AIM
To identify and characterize cancer stem cells (CSC) in moderately differentiated buccal mucosa squamous cell carcinoma (MDBMSCC).
METHODS
Four micrometer-thick, formalin-fixed, paraffin-embedded MDBMSCC samples from six patients underwent 3,3-diaminobenzidine (DAB) immunohistochemical (IHC) staining for the embryonic stem cell (ESC) markers, NANOG, OCT4, SALL4, SOX2, and pSTAT3; cancer stem cell marker, CD44; squamous cell carcinoma (SCC) marker, EMA; and endothelial marker, CD34. The transcriptional activities of the genes encoding NANOG, OCT4, SOX2, SALL4, STAT3, and CD44 were studied using NanoString gene expression analysis and colorimetric in situ hybridization (CISH) for NANOG, OCT4, SOX2, SALL4, and STAT3.
RESULTS
Diaminobenzidine and immunofluorescent (IF) IHC staining demonstrated the presence of (1) an EMA(+)/CD44(+)/SOX2(+)/SALL4(+)/OCT4(+)/pSTAT3(+)/NANOG(+) CSC subpopulation within the tumor nests; (2) an EMA(-)/CD44(-)/CD34(-)/SOX2(+)/OCT4(+)/pSTAT3(+)/NANOG(+) subpopulation within the stroma between the tumor nests; and (3) an EMA(-)/CD44(-)/CD34(+)/SOX2(+)/SALL4(+)/OCT4(+)/pSTAT3(+)/NANOG(+) subpopulation on the endothelium of the microvessels within the stroma. The expression of CD44, SOX2, SALL4, OCT4, pSTAT3, and NANOG was confirmed by the presence of mRNA transcripts, using NanoString analysis and NANOG, OCT4, SOX2, SALL4, and STAT3 by CISH staining.
CONCLUSION
This study demonstrated a novel finding of three separate CSC subpopulations within MDBMSCC: (1) within the tumor nests expressing EMA, CD44, SOX2, SALL4, OCT4, pSTAT3, and NANOG; (2) within the stroma expressing SOX2, SALL4, OCT4, pSTAT3, and NANOG; and (3) on the endothelium of the microvessels within the stroma expressing CD34, SOX2, SALL4, OCT4, pSTAT3, and NANOG.
目的
鉴定和表征中度分化的颊黏膜鳞状细胞癌（MDBMSCC）中的癌症干细胞（CSC）。
方法
对来自6例患者的4微米厚、福尔马林固定、石蜡包埋的MDBMSCC样本进行3,3-二氨基联苯胺（DAB）免疫组织化学（IHC）染色，检测胚胎干细胞（ESC）标志物NANOG、OCT4、SALL4、SOX2和pSTAT3；癌症干细胞标志物CD44；鳞状细胞癌（SCC）标志物EMA；以及内皮标志物CD34。使用NanoString基因表达分析和针对NANOG、OCT4、SOX2、SALL4和STAT3的比色原位杂交（CISH）研究编码NANOG、OCT4、SOX2、SALL4、STAT3和CD44的基因的转录活性。
结果
二氨基联苯胺和免疫荧光（IF）免疫组织化学染色显示存在：（1）肿瘤巢内的EMA(+)/CD44(+)/SOX2(+)/SALL4(+)/OCT4(+)/pSTAT3(+)/NANOG(+)癌症干细胞亚群；（2）肿瘤巢之间基质内的EMA(-)/CD44(-)/CD34(-)/SOX2(+)/OCT4(+)/pSTAT3(+)/NANOG(+)亚群；以及（3）基质内微血管内皮上的EMA(-)/CD44(-)/CD34(+)/SOX2(+)/SALL4(+)/OCT4(+)/pSTAT3(+)/NANOG(+)亚群。通过NanoString分析检测mRNA转录本以及通过CISH染色检测NANOG、OCT4、SOX2、SALL4和STAT3，证实了CD44、SOX2、SALL4、OCT4、pSTAT3和NANOG的表达。
结论
本研究在MDBMSCC中发现了三个不同的癌症干细胞亚群这一新颖发现：（1）肿瘤巢内表达EMA、CD44、SOX2、SALL4、OCT4、pSTAT3和NANOG；（2）基质内表达SOX2、SALL4、OCT4、pSTAT3和NANOG；以及（3）基质内微血管内皮上表达CD34、SOX2、SALL4、OCT4、pSTAT3和NANOG。
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