Self-renewal and chemotherapy resistance of p75NTR positive cells in esophageal squamous cell carcinomas.
Self-renewal and chemotherapy resistance of p75NTR positive cells in esophageal squamous cell carcinomas.
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食管鳞状细胞癌中p75NTR阳性细胞的自我更新和化疗耐药性。
DOI：
10.1186/1471-2407-9-9
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发表时间：
2009-01-10
期刊：
影响因子：
3.8
通讯作者：
Xu, Zhi-Yun
中科院分区：
文献类型：
--
作者：
Huang, Sheng-Dong;Yuan, Yang;Liu, Xiao-Hong;Gong, De-Jun;Bai, Chen-Guang;Wang, Feng;Luo, Jun-Hui;Xu, Zhi-Yun
p75NTR 已用于分离食管和角膜上皮干细胞。在本研究中，我们研究了p75NTR在食管鳞状细胞癌（ESCC）中的表达，并探讨了p75NTR+细胞的生物学特性。通过免疫组织化学评估 ESCC 中 p75NTR 的表达。通过荧光激活细胞分选来分离 4 个 ESCC 细胞系的 p75NTR+ 和 p75NTR- 细胞。通过实时定量逆转录-PCR 确定p75NTR+ 和p75NTR- 细胞之间差异表达的基因。通过成球实验、DDP敏感性实验、64铜累积实验和致瘤性分析来测定p75NTR+细胞的自我更新能力、化疗耐药性和致瘤性。在 ESCC 标本中，发现 p75NTR 主要局限于未成熟细胞，在终末分化的细胞中不存在。 Eca109和3个新建立的ESCC细胞系中p75NTR+细胞的比例为1.6%~3.7%。与干细胞自我更新相关的 Bmi-1 表达在 p75NTR+ 细胞中显着较高。 p63 是角质形成细胞干细胞中鉴定的一种标记物，主要局限于 p75NTR+ 细胞。与顺铂 (DDP) 耐药相关的 CTR1 表达在 p75NTR+ 细胞中显着降低。 p75NTR+细胞中分化标志物的表达水平较低，例如外皮蛋白、细胞角蛋白13、β1-整合素和β4-整合素。此外，p75NTR+细胞产生p75NTR+和p75NTR-细胞，并在补充有生长因子的无血清培养基中形成非贴壁的球形簇。此外，发现p75NTR+细胞比p75NTR-细胞对DDP更具抵抗力并且表现出更低的64铜积累。我们的结果表明p75NTR+细胞具有CSC的一些特征，即自我更新和化疗耐药性。 p75NTR+细胞的化疗抵抗可能归因于CTR1表达的降低。
p75NTR has been used to isolate esophageal and corneal epithelial stem cells. In the present study, we investigated the expression of p75NTR in esophageal squamous cell carcinoma (ESCC) and explored the biological properties of p75NTR+ cells. p75NTR expression in ESCC was assessed by immunohistochemistry. p75NTR+ and p75NTR- cells of 4 ESCC cell lines were separated by fluorescence-activated cell sorting. Differentially expressed genes between p75NTR+ and p75NTR- cells were determined by real-time quantitative reverse transcription-PCR. Sphere formation assay, DDP sensitivity assay, 64copper accumulation assay and tumorigenicity analysis were performed to determine the capacity of self-renewal, chemotherapy resistance and tumorigenicity of p75NTR+ cells. In ESCC specimens, p75NTR was found mainly confined to immature cells and absent in cells undergoing terminal differentiation. The percentage of p75NTR+ cells was 1.6%–3.7% in Eca109 and 3 newly established ESCC cell lines. The expression of Bmi-1, which is associated with self-renewal of stem cells, was significantly higher in p75NTR+ cells. p63, a marker identified in keratinocyte stem cells, was confined mainly to p75NTR+ cells. The expression of CTR1, which is associated with cisplatin (DDP)-resistance, was significantly decreased in p75NTR+ cells. Expression levels of differentiation markers, such as involucrin, cytokeratin 13, β1-integrin and β4-integrin, were lower in p75NTR+ cells. In addition, p75NTR+ cells generated both p75NTR+ and p75NTR- cells, and formed nonadherent spherical clusters in serum-free medium supplemented with growth factors. Furthermore, p75NTR+ cells were found to be more resistant to DDP and exhibited lower 64copper accumulation than p75NTR- cells. Our results demonstrated that p75NTR+ cells possess some characteristics of CSCs, namely, self-renewal and chemotherapy resistance. Chemotherapy resistance of p75NTR+ cells may probably be attributable to decreased expression of CTR1.
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影响因子：
64.8
作者：
Mills, AA;Zheng, BH;Bradley, A
通讯作者：
Bradley, A
影响因子：
3.4
作者：
Qi, Hong;Li, De-Quan;Pflugfelder, Stephen C.
通讯作者：
Pflugfelder, Stephen C.
影响因子：
11.2
作者：
Li, Chenwei;Heidt, David G.;Simeone, Diane M.
通讯作者：
Simeone, Diane M.
影响因子：
4.8
作者：
Mitsutake, Norisato;Iwao, Atsuhiko;Yamashita, Shunichi
通讯作者：
Yamashita, Shunichi
影响因子：
29.4
作者：
Ma, Stephanie;Chan, Kwok-Wah;Guan, Xin-Yuan
通讯作者：
Guan, Xin-Yuan