Malignant ascites-derived organoid (MADO) cultures for gastric cancer in vitro modelling and drug screening
Malignant ascites-derived organoid (MADO) cultures for gastric cancer in vitro modelling and drug screening
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DOI：
10.1007/s00432-019-03004-z
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发表时间：
2019-10-09
影响因子：
3.6
通讯作者：
Zhan, Xianbao
中科院分区：
文献类型：
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作者：
Li, Jie;Xu, Huawei;Zhan, Xianbao
目的恶性腹水（MA）是晚期胃癌合并腹膜癌的常见表现，预后较差。然而，缺乏能够真实再现腹水肿瘤细胞特征的体外模型阻碍了相关研究。肿瘤类器官已成为肿瘤研究和药物筛选的一个强大的体外模型。因此，我们旨在从胃癌恶性腹水中生成三维体外类器官培养物，用于疾病建模和药物筛选。方法从胃癌患者的MA肿瘤细胞中生成11个mdos。我们通过免疫组织化学和全外显子组测序对mdos和原始MA肿瘤细胞的组织病理学进行了比较。为了评估MADOs在体外疾病模型中的功能，我们测试了MADOs是否可以用于药物敏感性筛选。结果建立了11个人胃癌组织的MADO培养物。mdo表现出不同的生长特征和形态。MADO培养保存了相应的MA肿瘤细胞的组织学结构和基因组景观。mado对标准化疗药物表现出异质反应。结论我们获得了MA肿瘤细胞的mdos模型特征和突变基因。MADO对常规化疗的广泛内在反应表明，MADO可用于药物筛选。
Purpose Malignant ascites (MA) is a common manifestation in advanced gastric cancer with peritoneal carcinomatosis and usually indicates a poor prognosis. However, lack of in vitro models that can faithfully recapitulate the characteristics of tumour cells in ascites hinders related researches. Tumour organoids have emerged as a robust in vitro model for tumour research and drug screening. Hence, we aimed to generate a 3-D in vitro organoid cultures from malignant ascites of gastric cancer for disease modelling and drug screening. Methods Eleven MADOs were generated from the MA tumour cells of gastric cancer patients. We made comparisons between MADOs and original MA tumour cells in histopathology by immunohistochemistry and genomics by whole-exome sequencing. In order to evaluate MADOs as functional in vitro disease models, we tested whether MADOs could be used for drug sensitivity screens. Results Eleven MADO cultures from human gastric cancer were established. MADOs demonstrated divergent growth characteristics and morphologies. MADO cultures preserve the histological architecture, genomic landscape of the corresponding MA tumour cells. MADOs exhibited heterogeneous responses to standard-of-care chemotherapeutics. Conclusions We generated MADOs modelling characteristics and mutated genes of MA tumour cells. A broad range of intrinsic MADO response to conventional chemotherapeutics suggests MADOs are amenable to drug screening.