Preliminary research on breast cancer organoids as a radiobiological model
Li Li1,2, Han Zhongbin3, Chen Hongsheng3, Liang Shanshan1, Wang Ruoyu2
1Key Laboratory of High-Throughput Screening or Targeted Drug Transformation of Molecular Markers of Breast and Digestive Tumors of Liaoning Province, Dalian 116001, China; 2Department of Oncology, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, China; 3Department of Thyroid and Breast Surgery, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, China
Abstract：Objective To construct breast cancer organoid culture system and conduct histological characterization and preliminary radiobiological characteristics study. Methods Different molecular types of breast cancer cell lines and patient-derived tumor cells were cultured in vitro to form breast cancer organoids and characterize their tissue structure. In addition, Ki-67, ER, PR and Her2 markers were evaluated by immunohistochemical staining. Breast cancer organoids were irradiated with 4Gy and 8Gy. The numbe and diameter changes of breast cancer organoids at 0, 24, 48 and 96h after irradiation were observed to evaluate the irradiation-induced damage to the organoids. Results Breast cancer cell lines and patient-derived tissues formed organoid structures at 6d. HE staining showed the microstructures, and the expression profile of markers was spatially heterogeneous. The expression patterns of markers were similar between patient-derived organoids and original tumor tissues. Irradiation of MCF-7 breast cancer organoids led to growth arrested, and some of the formed organoids collapsed and the proliferating trend gradually recovered from 48h to 96h. MDA-MB-231 breast tumor organoids showed radioresistance, growth arrested, but the structures remained intact, the recovery trend was still not observed at 96h. The tissue-derived organoids from triple-negative patients also showed radiation tolerance. After irradiation, the organoids continued to grow without significant structural changes, whereas the growth trend was significantly smaller than that in the non-irradiated group. Conclusions Breast cancer organoids formed by in vitro culture of breast cancer cells from different sources and different molecular types have microstructure and heterogeneity, which can reflect the expression of source tissue markers and show different radioresistance. Organoids derived from triple-negative breast cancer are more resistant to irradiation.
Li Li,Han Zhongbin,Chen Hongsheng et al. Preliminary research on breast cancer organoids as a radiobiological model[J]. Chinese Journal of Radiation Oncology, 2022, 31(6): 556-561.
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