Establishment of PDX‐derived salivary adenoid cystic carcinoma cell lines using organoid culture method
Establishment of PDX‐derived salivary adenoid cystic carcinoma cell lines using organoid culture method
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类器官培养法建立PDX源性涎腺腺样囊性癌细胞系
DOI：
10.1002/ijc.33315
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发表时间：
2020-09
影响因子：
6.4
通讯作者：
Kentaro Takada;Yoshihiro Aizawa;D. Sano;R. Okuda;K. Sekine;Y. Ueno;S. Yamanaka;Jun Aoyama;Kaname Sato;Tatsu Kuwahara;T. Hatano;Hideaki Takahashi;Yasuhiro Arai;G. Nishimura;H. Taniguchi;N. Oridate
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文献类型：
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作者：
Kentaro Takada;Yoshihiro Aizawa;D. Sano;R. Okuda;K. Sekine;Y. Ueno;S. Yamanaka;Jun Aoyama;Kaname Sato;Tatsu Kuwahara;T. Hatano;Hideaki Takahashi;Yasuhiro Arai;G. Nishimura;H. Taniguchi;N. Oridate
建立一个可靠的临床前模型系统，展示唾液腺腺样囊性癌（ACC）的分子特征，由于缺乏稳定的细胞培养物，其生物学特性仍不清楚。为了开发新的 ACC 体外和体内模型，应用了近年来在其他恶性肿瘤中引起关注的类器官培养和患者来源的肿瘤异种移植（PDX）技术。来自手术切除的唾液 ACC 的肿瘤标本用于制备 PDX 和类器官培养物。患者来源或 PDX 来源的类器官原位移植到 NSG 小鼠的下颌下腺中，并评估了这些组织学。评估 PDX 衍生的类器官细胞是否存在 MYB 介导的融合基因，并进行体外药物敏感性测定。在三维培养中成功生成了人类 ACC 衍生的类器官，并证实了这些细胞通过原位注射形成肿瘤的能力。还建立了来自两个个体 ACC PDX 肿瘤的短期类器官细胞培养物，其保持了原始亲代肿瘤和 PDX 肿瘤的特征性 MYBL1 易位和组织学特征。最后，使用三种不同的试剂证实了对这些短期培养细胞的药物敏感性测试的建立。这是第一个报告一种生成人类 ACC 衍生类器官作为体外和体内癌症模型的方法，为理解 ACC 生物学和为 ACC 患者创建个性化治疗设计提供了见解。
To generate a reliable preclinical model system exhibiting the molecular features of salivary adenoid cystic carcinoma (ACC) whose biology is still unclear due to the paucity of stable cell cultures. To develop new in vitro and in vivo models of ACC, the techniques of organoid culture and patient‐derived tumor xenograft (PDX), which have attracted attention in other malignancies in recent years, were applied. Tumor specimens from surgically resected salivary ACC were proceeded for the preparation of PDX and organoid culture. The orthotopic transplantation of patient‐derived or PDX‐derived organoids was demonstrated into submandibular glands of NSG mice and those histology was evaluated. PDX‐derived organoid cells were evaluated for the presence of MYB‐mediated fusion genes and proceeded for in vitro drug sensitivity assay. Human ACC‐derived organoids were successfully generated in three‐dimensional culture and confirmed the ability of these cells to form tumors by orthotopic injection. Short‐term organoid cell cultures from two individual ACC PDX tumors were also established that maintain the characteristic MYBL1 translocation and histological features of the original parent and PDX tumors. Finally, the establishment of drug sensitivity tests on these short‐term cultured cells was confirmed using three different agents. This is the first to report an approach for the generation of human ACC‐derived organoids as in vitro and in vivo cancer models, providing insights into understanding of the ACC biology and creating personalized therapy design for patients with ACC.