Cancer-initiating cells derived from established cervical cell lines exhibit stem-cell markers and increased radioresistance.
Cancer-initiating cells derived from established cervical cell lines exhibit stem-cell markers and increased radioresistance.
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DOI：
10.1186/1471-2407-12-48
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发表时间：
2012-01-28
期刊：
影响因子：
3.8
通讯作者：
García-Carrancá A
中科院分区：
文献类型：
--
作者：
López J;Poitevin A;Mendoza-Martínez V;Pérez-Plasencia C;García-Carrancá A
癌症起始细胞（CIC）被认为是产生转移和对治疗产生抗性的原因。越来越多的证据表明，CIC存在于不同的人类癌症及其衍生的细胞系中。很少有研究涉及宫颈癌中CIC的特征。我们从四种最著名的宫颈肿瘤人类细胞系中识别出CIC的生物学特征。(HeLa，SiHa，Ca Ski，C-4 I）。在干细胞条件下将细胞培养为球体。流式细胞术检测CD 34、CD 49 f和CD 133抗原的表达，Hoechst 33342染色鉴定侧群（SP）。应用磁性和荧光激活细胞分选来富集和纯化用于评估裸鼠致瘤性的群体。在标准条件下进行cDNA微阵列分析和体外辐射抗性测定。富含球状体的CIC能够在nu-nu小鼠中产生可再现的肿瘤表型并连续繁殖。注射1 × 103个分离的球状体细胞在大多数动物中诱导肿瘤，而注射1 × 105个单层细胞仍无致瘤性。球形来源的CIC表达CD 49 f表面标记物。HeLa和SiHa球状体细胞的基因谱分析显示女性生殖系统特征性的CIC标志物上调。重要的是，上皮间充质（EMT）转型相关的标志物被发现高度表达的球体细胞。更重要的是，基因表达分析表明，辐射抗性所需的基因也上调，包括双链断裂（DSB）DNA修复机制和活性氧（ROS）代谢的组件。剂量依赖性辐射测定表明，确实CIC富集的人口表现出增加的抵抗电离辐射（IR）。我们表征了在四种众所周知的人类癌症衍生细胞系（HeLa、SiHa、Ca Ski和C-4 I）中发现的自我更新CIC亚群，并发现它们表达干细胞、EMT和放射抗性的特征性标志物。CIC表现出比分化细胞更高程度的辐射抗性的事实表明，特异性检测和靶向CIC对于来自子宫颈的肿瘤的治疗可能是非常有价值的。
Cancer-initiating cells (CICs) are proposed to be responsible for the generation of metastasis and resistance to therapy. Accumulating evidences indicates CICs are found among different human cancers and cell lines derived from them. Few studies address the characteristics of CICs in cervical cancer. We identify biological features of CICs from four of the best-know human cell lines from uterine cervix tumors. (HeLa, SiHa, Ca Ski, C-4 I). Cells were cultured as spheres under stem-cell conditions. Flow cytometry was used to detect expression of CD34, CD49f and CD133 antigens and Hoechst 33342 staining to identify side population (SP). Magnetic and fluorescence-activated cell sorting was applied to enrich and purify populations used to evaluate tumorigenicity in nude mice. cDNA microarray analysis and in vitro radioresistance assay were carried out under standard conditions. CICs, enriched as spheroids, were capable to generate reproducible tumor phenotypes in nu-nu mice and serial propagation. Injection of 1 × 103 dissociated spheroid cells induced tumors in the majority of animals, whereas injection of 1 × 105 monolayer cells remained nontumorigenic. Sphere-derived CICs expressed CD49f surface marker. Gene profiling analysis of HeLa and SiHa spheroid cells showed up-regulation of CICs markers characteristic of the female reproductive system. Importantly, epithelial to mesenchymal (EMT) transition-associated markers were found highly expressed in spheroid cells. More importantly, gene expression analysis indicated that genes required for radioresistance were also up-regulated, including components of the double-strand break (DSB) DNA repair machinery and the metabolism of reactive oxygen species (ROS). Dose-dependent radiation assay indicated indeed that CICs-enriched populations exhibit an increased resistance to ionizing radiation (IR). We characterized a self-renewing subpopulation of CICs found among four well known human cancer-derived cell lines (HeLa, SiHa, Ca Ski and C-4 I) and found that they express characteristic markers of stem cell, EMT and radioresistance. The fact that CICs demonstrated a higher degree of resistance to radiation than differentiated cells suggests that specific detection and targeting of CICs could be highly valuable for the therapy of tumors from the uterine cervix.
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影响因子：
3.6
作者：
Gargett, Caroline E.;Schwab, Kjiana E.;Wu, Di
通讯作者：
Wu, Di
DOI：
10.1073/pnas.0703478104
发表时间：
2007-06-12
影响因子：
11.1
作者：
Dalerba, Piero;Dylla, Scott J.;Clarke, Michael F.
通讯作者：
Clarke, Michael F.
影响因子：
3.7
作者：
Fothergill, Thomas;McMillan, Nigel A. J.
通讯作者：
McMillan, Nigel A. J.
影响因子：
29.4
作者：
Levin TG;Powell AE;Davies PS;Silk AD;Dismuke AD;Anderson EC;Swain JR;Wong MH
通讯作者：
Wong MH
影响因子：
11.2
作者：
Collins, AT;Berry, PA;Maitland, NJ
通讯作者：
Maitland, NJ