Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Hum Cell. 2023 May;36(3):1135-1146. doi: 10.1007/s13577-023-00882-x. Epub 2023 Mar 3.
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.
放射抗拒是导致宫颈癌 (CC) 患者放疗失败的主要原因，也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异质性，这给放射抗拒研究带来了挑战。与此同时，条件重编程 (CR) 维持了肿瘤内异质性和复杂性，以及原始细胞和组织的基因组和临床特征。通过 CR 条件从患者标本中开发了三种放射抗拒和两种放射敏感的原发性 CC 细胞系，并通过免疫荧光、生长动力学、克隆形成测定、异种移植和免疫组织化学验证了它们的特征。CR 细胞系具有与原始肿瘤组织相同的特征，并在体外和体内保持放射敏感性，同时根据单细胞 RNA 测序分析也保持了肿瘤内异质性。进一步研究发现，与放射敏感的 CR 细胞系相比，放射抗拒的 CR 细胞系中有 20.83%的细胞聚集在对辐射敏感的 G2/M 细胞周期阶段，而放射敏感的 CR 细胞系中有 38.1%的细胞聚集在 G2/M 细胞周期阶段。本研究通过 CR 建立了三种放射抗拒和两种放射敏感的 CC 细胞系，这将有助于进一步研究 CC 中的放射敏感性。本研究可能为 CC 中放射抗拒的发展和潜在治疗靶点的研究提供了一个理想的模型。
