Insights into the characteristics of primary radioresistant cervical cancer using single-cell transcriptomics.
Insights into the characteristics of primary radioresistant cervical cancer using single-cell transcriptomics.
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DOI：
10.1007/s13577-023-00882-x
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发表时间：
2023-05
期刊：
影响因子：
4.3
通讯作者：
Zhao, Yingchao
中科院分区：
文献类型：
--
作者：
Xing, Biyuan;Pu, Congli;Chen, Yunshang;Sheng, Yuhan;Zhang, Baofang;Cui, Jie;Wu, Gang;Zhao, Yingchao
关键词：
放射抗性是宫颈癌（CC）患者放疗失败的主要原因，宫颈癌是全球女性癌症死亡的第四大常见原因。传统的CC细胞系失去了肿瘤内的异质性，对放射抗性研究提出了挑战。同时，条件重编程（CR）保持了肿瘤内的异质性和复杂性，以及原始细胞和组织的基因组和临床特征。三个放射抗性和两个放射敏感性的原代CC细胞系CR条件下从患者标本，其特征进行了验证，通过免疫荧光，生长动力学，克隆形成试验，异种移植，和免疫组化。CR细胞系与原始肿瘤组织具有同源性特征，并在体外和体内保持放射敏感性，同时根据单细胞RNA测序分析还保持肿瘤内异质性。经进一步研究，20.83%的细胞在放射抗性CR细胞系中聚集在G2/M细胞周期期，这是对辐射敏感的，相比之下，38.1%的细胞在放射敏感CR细胞系中。本研究通过CR技术建立了3株放射抗性和2株放射敏感性CC细胞系，为进一步研究CC的放射敏感性奠定了基础。本研究为研究CC的放射抗性和潜在的治疗靶点提供了一个理想的模型。在线版本包含补充材料，可通过10.1007/s13577-023-00882-x获得。
Radioresistance is a major cause of radiotherapy failure among patients with cervical cancer (CC), the fourth most common cause of cancer mortality in women worldwide. Traditional CC cell lines lose intra-tumoral heterogeneity, posing a challenge for radioresistance research. Meanwhile, conditional reprogramming (CR) maintains intra-tumoral heterogeneity and complexity, as well as the genomic and clinical characteristics of original cells and tissues. Three radioresistant and two radiosensitive primary CC cell lines were developed under CR conditions from patient specimens, and their characteristics were verified via immunofluorescence, growth kinetics, clone forming assay, xenografting, and immunohistochemistry. The CR cell lines had homogenous characteristics with original tumor tissues and maintained radiosensitivity in vitro and in vivo, while also maintaining intra-tumoral heterogeneity according to single-cell RNA sequencing analysis. Upon further investigation, 20.83% of cells in radioresistant CR cell lines aggregated in the G2/M cell cycle phase, which is sensitive to radiation, compared to 38.1% of cells in radiosensitive CR cell lines. This study established three radioresistant and two radiosensitive CC cell lines through CR, which will benefit further research investigating radiosensitivity in CC. Our present study may provide an ideal model for research on development of radioresistance and potential therapeutic targets in CC. The online version contains supplementary material available at 10.1007/s13577-023-00882-x.
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DOI：
10.1038/nrclinonc.2015.120
发表时间：
2015-09
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
Schaue D;McBride WH
通讯作者：
McBride WH
影响因子：
3.9
作者：
Li H;Wu X;Cheng X
通讯作者：
Cheng X
影响因子：
4.7
作者：
Alkhilaiwi F
通讯作者：
Alkhilaiwi F
影响因子：
5
作者：
Li Y;Guo D;Zhang Y;Wang L;Sun T;Li Z;Zhang X;Wang S;Chen Y;Wu A
通讯作者：
Wu A
影响因子：
64.8
作者：
Medema, RH;Kops, GJPL;Burgering, BMT
通讯作者：
Burgering, BMT