Tumor initiating cells in esophageal squamous cell carcinomas express high levels of CD44.

Tumor initiating cells in esophageal squamous cell carcinomas express high levels of CD44.
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食管鳞状细胞癌中的肿瘤起始细胞表达高水平的 CD44。

DOI:
10.1371/journal.pone.0021419
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Xie D
Xie D
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zhao JS;Li WJ;Ge D;Zhang PJ;Li JJ;Lu CL;Ji XD;Guan DX;Gao H;Xu LY;Li EM;Soukiasian H;Koeffler HP;Wang XF;Xie D

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食管鳞状细胞癌(ESCC)是食管癌的一个主要亚型,在亚洲引起显著的发病率和死亡率。该病的发生和发展机制尚不清楚。肿瘤起始细胞(Tumor initiating cells,TIC)是一类具有自我更新能力的细胞亚群,能够驱动肿瘤的发生和发展。越来越多的证据表明TIC存在于多种肿瘤中。然而,食管癌中TIC的识别和表征仍然是难以捉摸的。为了鉴定ESCC中的TIC,使用包括两个原代细胞的ESCC细胞系来筛选合适的表面标记。采用集落形成试验、耐药试验和免疫缺陷小鼠致瘤性试验对食管鳞癌中TIC进行鉴定。我们发现,只有CD 44表达与ESCC细胞系的致瘤性相关。全反式维甲酸诱导食管鳞癌细胞分化后,CD 44表达下降。与低表达CD 44的ESCC细胞相比,具有高表达CD 44的FACS分离的细胞亚群在体外显示出增加的集落形成和耐药性,以及在NOD/SICD小鼠中显著增强的致瘤性。我们的研究发现了一种新的TIC表面标记物,CD 44,它可以用来有效地富集食管鳞癌中的TIC。这些发现将有助于进一步研究这些细胞和探索治疗方法。
Esophageal Squamous Cell Carcinoma (ESCC) is a major subtype of esophageal cancer causing significant morbility and mortality in Asia. Mechanism of initiation and progression of this disease is unclear. Tumor initiating cells (TICs) are the subpopulation of cells which have the ability to self-renew, as well as, to drive initiation and progression of cancer. Increasing evidence has shown that TICs exist in a variety of tumors. However, the identification and characterization of TICs in esophageal carcinoma has remained elusive. to identify TICs in ESCC, ESCC cell lines including two primary cells were used for screening suitable surface marker. Then colony formation assay, drug resistant assay and tumorigenicity assay in immune deficient mice were used to characterize TICs in ESCC. We found that just the CD44 expression correlated with tumorigenicity in ESCC cell lines. And then induced differentiation of ESCC cells by all-trans retinoic acid treatment led to decreased expression of CD44. The FACS isolated cell subpopulations with high CD44 expression showed increased colony formation and drug resistance in vitro, as well as significantly enhanced tumorigenicity in NOD/SICD mice, as compared to the low expressing CD44 ESCC cells. our study has discovered a novel TIC surface marker, CD44, which can be utilized to enrich efficiently the TICs in ESCC. These findings will be useful for further studies of these cells and exploring therapeutic approaches.
食管鳞状细胞癌中p75NTR阳性细胞的自我更新和化疗耐药性。
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