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作 者:刘晓青 李学超 马洁 张继泉 朱云平 LIU Xiaoqing;LI Xuechao;MA Jie;ZHANG Jiquan;ZHU Yunping(School of Life Sciences,Hebei University,Baoding 071002,Hebei,China;State Key Laboratory of Medical Proteomics,Beijing Proteome Research Center,National Center for Protein Sciences(Beijing),Beijing Institute of Lifeomics,Academy of Military Medical Sciences,Beijing 102206,China;The Fifth Medical Center of the General Hospital of the People’s Liberation Army,Beijing 100700,China)
机构地区:[1]河北大学生命科学学院,河北保定071002 [2]军事医学研究院生命组学研究所国家蛋白质科学中心(北京)北京蛋白质组研究中心医学蛋白质组全国重点实验室,北京102206 [3]解放军总医院第五医学中心,北京100700
出 处:《生物工程学报》2024年第7期2211-2222,共12页Chinese Journal of Biotechnology
基 金:国家自然科学基金(32270697)。
摘 要:肾盂癌是一种较为常见的上尿路上皮癌,由于缺乏理想的体外模型,严重阻碍了该类疾病治疗策略研究的进展。本研究基于肾盂癌患者来源肿瘤组织样本,建立肾盂癌类器官培养方法,并基于肾盂癌类器官构建肿瘤化疗药物反应模型。通过免疫组化和荧光实验证实,培养获得的肾盂癌类器官核异型性明显,与亲本肾盂癌组织一致;肾盂癌类器官中肿瘤标志分子CD44和细胞增殖标志分子Ki67均呈强阳性,表明类器官富集肿瘤干细胞,具有较强增殖能力。药物反应实验显示肾盂癌类器官对吡柔比星高度敏感,杀伤作用明显。本研究成功建立了肾盂癌类器官体外培养体系,并进行了初步体外药敏试验,为以肾盂癌为代表的上尿路上皮癌的个体化诊疗提供了新的体外实验模型。Renal pelvic carcinoma is a common upper urothelial cancer.The lack of an ideal in vitro model seriously hinders the research progress in the treatment for this disease.This study established a pipeline for the culture of renal pelvic carcinoma organoids based on the tumor tissue samples derived from the patients and tested the organoids to chemotherapeutic drugs.The results of immunohistochemistry and fluorescence experiments confirmed that the renal pelvic carcinoma organoids obtained from culture presented obvious nuclear heteromorphism,which was consistent with the tissue samples from renal pelvic carcinoma patients.The tumor marker molecule CD44 and the cell proliferation marker molecule Ki67 were positive in the organoids,indicating that the organoids were enriched with tumor stem cells and had strong proliferative ability.The renal pelvic carcinoma organoids were highly sensitive to pirarubicin,which had obvious killing effects.In brief,this study successfully established an in vitro model of renal pelvic cancer organoids and tested the sensitivity of the model to chemotherapeutic drugs.The results provide a new laboratory model for the individualized diagnosis and treatment of epithelial carcinomas represented by renal pelvic carcinoma.
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