Phenotypic heterogeneity of 2D organoid reflects clinical tumor characteristics
Phenotypic heterogeneity of 2D organoid reflects clinical tumor characteristics
复制标题
DOI：
10.1016/j.bbrc.2019.03.173
复制
发表时间：
2019-05-28
影响因子：
3.1
通讯作者：
Miyoshi, Norikatsu
中科院分区：
文献类型：
--
作者：
Fujino, Shiki;Ito, Aya;Miyoshi, Norikatsu
与癌细胞系不同，肿瘤和原代培养细胞表现出表型异质性。虽然在三维（3D）凝胶中建立类器官的方法是众所周知的，但其生长速度比二维（2D）培养的细胞慢，并且需要添加许多生态位因子。在本研究中，我们以可重复的方式在2D培养中建立了原代培养的类器官（2D organoid; 2D0），具有临床表型异质性。2D0含有表达CD44和CD133的癌症干细胞（CSCs）。加入碱性成纤维细胞生长因子和转化生长因子- β作为生态位因子是建立2D0和维持CSC群体的必要条件。建立的2D0具有充分的增殖，可以转移到3D培养。2D0诱导的异种移植物形态学分析反映了亲本肿瘤的分化，并且2D0中的基因表达与亲本肿瘤相似。体外药敏分析采用2D0反应个体临床病程。2D0是一种体外个体肿瘤模型，药物敏感性评估结果可能为个性化医疗中引入临床化疗药物提供参考。(C) 2019 Elsevier Inc.版权所有。
Unlike cancer cell lines, tumors and primary cultured cells exhibit phenotypic heterogeneity. Although methods for establishing organoids within three-dimensional (3D) gels are well-known, the growth is slower than that of two-dimensional (2D) cultured cells and many niche factors need to be added. In this study, we established primary cultured organoid in 2D culture (2D organoid; 2D0) in a reproducible manner and with clinical phenotypic heterogeneity. The 2D0 contained cancer stem cells (CSCs) expressing CD44 and CD133. The addition of basic fibroblast growth factor and transforming growth factor-beta as niche factors was necessary to establish the 2D0 and maintain the CSC population. The established 2D0 showed sufficient proliferation, and the culture could be transferred to the 3D culture. Morphological analysis of the xenograft induced by 2D0 reflected parental tumor differentiation, and gene expression in the 2D0 was similar to that in the parental tumor. In vitro drug sensitivity analysis using the 2D0 reflected individual clinical courses. The 2D0 is an in vitro personal cancer model, and the results of the drug sensitivity assessment may be useful for introducing clinical chemotherapy agents in personalized medicine. (C) 2019 Elsevier Inc. All rights reserved.