结直肠癌肝转移类器官保留原发肿瘤的特征并获得化疗耐药性。
Colorectal cancer liver metastases organoids retain characteristics of original tumor and acquire chemotherapy resistance.
作者信息
Buzzelli Jon N, Ouaret Djamila, Brown Graham, Allen Philip D, Muschel Ruth J
机构信息
Old Road Research Campus Building, Department of Oncology, University of Oxford, Oxford, UK.
Cancer and Immunogenetics Laboratory, Weatherall Institute of Molecular Medicine, Department of Oncology, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK.
出版信息
Stem Cell Res. 2018 Mar;27:109-120. doi: 10.1016/j.scr.2018.01.016. Epub 2018 Jan 28.
BACKGROUND
Colorectal cancer (CRC) liver metastasis is highly unfavorable for patient outcome and is a leading cause of cancer-related death. Pre-clinical research of CRC liver metastasis predominately utilizes CRC cell lines grown in tissue culture. Here, we demonstrate that CRC liver metastases organoids derived from human specimens recapitulate some aspects of human disease.
METHODS
Human CRC liver metastases pathological specimens were obtained following patient consent. Tumor disaggregates were plated and organoids were allowed to expand. CRC markers were identified by immunofluorescence. Stem cell genes were analysed by QPCR and flow cytometry. Response to drug therapy was quantified using time-lapse imaging and MATLAB analysis.
RESULTS
Organoids showed global expression of the epithelial marker, EpCAM and the adenocarcinoma marker, CEA CAM1. Flow cytometry analysis demonstrated that organoids express the stem cell surface markers CD24 and CD44. Finally, we demonstrated that CRC liver metastases organoids acquire chemotherapy resistance and can be utilized as surrogates for drug testing.
CONCLUSION
These data demonstrate that CRC liver metastases organoids recapitulate some aspects of human disease and may provide an invaluable resource for investigating novel drug therapies, chemotherapy resistance and mechanism of metastasis.
背景
结直肠癌（CRC）肝转移对患者预后极为不利，是癌症相关死亡的主要原因。CRC肝转移的临床前研究主要利用在组织培养中生长的CRC细胞系。在此，我们证明源自人类标本的CRC肝转移类器官概括了人类疾病的某些方面。
方法
在获得患者同意后获取人类CRC肝转移病理标本。将肿瘤解离物接种培养，使类器官得以扩增。通过免疫荧光鉴定CRC标志物。通过定量聚合酶链反应（QPCR）和流式细胞术分析干细胞基因。使用延时成像和MATLAB分析对药物治疗反应进行定量。
结果
类器官显示上皮标志物EpCAM和腺癌标志物CEA CAM1的整体表达。流式细胞术分析表明类器官表达干细胞表面标志物CD24和CD44。最后，我们证明CRC肝转移类器官获得化疗耐药性，可作为药物测试的替代物。
结论
这些数据表明CRC肝转移类器官概括了人类疾病的某些方面，可能为研究新型药物疗法、化疗耐药性和转移机制提供宝贵资源。
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