Characterization of ovarian cancer cell lines as in vivo models for preclinical studies.
Characterization of ovarian cancer cell lines as in vivo models for preclinical studies.
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DOI：
10.1016/j.ygyno.2016.05.028
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发表时间：
2016-08
影响因子：
4.7
通讯作者：
Annunziata CM
中科院分区：
文献类型：
--
作者：
Hernandez L;Kim MK;Lyle LT;Bunch KP;House CD;Ning F;Noonan AM;Annunziata CM
细胞系用于临床前工作的价值在于选择具有相似特征的细胞系。细胞系的选择通常基于患者病史、诊断时的组织学亚型、突变模式或信号传导途径。尽管最近的研究就卵巢癌细胞系的分子特征达成了共识，但关于体内致瘤性的数据仍然只是零星可用，阻碍了体外工作向异种移植模型的转化。我们将18个卵巢癌细胞系通过皮下、腹腔和卵巢囊内途径导入无胸腺裸鼠体内，观察6周内肿瘤的发展。我们还分析了细胞系基因表达，并根据其在皮下或腹膜内形成肿瘤的能力鉴定了差异表达的基因组。对代表性细胞系进一步进行蛋白质组学分析。卵巢癌细胞系在皮下、腹膜内或囊内植入小鼠体内时表现出不同的生长能力。虽然一些细胞系在SC和IP位置都生长良好，但其他细胞系显示出仅在一个位置生长的强烈倾向。基因表达谱表明，显示IP生长偏好的细胞系具有与原发性肿瘤更相似的基因表达模式。我们报告了17个人卵巢癌细胞系和一个小鼠细胞系在三个不同解剖位置的致瘤性，以及相关的基因网络。与分子特征相关的生长模式和组织病理学为研究界提供了宝贵的资源，并更好地指导体外研究细胞系的选择，以有效地转化为异种移植物测试。
The value of cell lines for pre-clinical work lies in choosing those with similar characteristics. Selection of cell lines is typically based on patient history, histological subtype at diagnosis, mutation patterns, or signaling pathways. Although recent studies established consensus regarding molecular characteristics of ovarian cancer cell lines, data on in vivo tumorigenicity remains only sporadically available, impeding translation of in vitro work to xenograft models. We introduced 18 ovarian cancer cell lines into athymic nude mice through subcutaneous, intraperitoneal, and ovary intrabursal routes, and observed tumor development over 6 weeks. We also profiled cell line gene expression and identified differentially expressed gene sets based on their ability to form tumors in the subcutaneous or intraperitoneal locations. Representative cell lines were further subjected to proteomic analyses. Ovarian cancer cell lines showed variable ability to grow in mice when implanted subcutaneous, intraperitoneal, or intrabursal. While some cell lines grew well in both SC and IP locations, others showed a strong propensity to grow in one location only. Gene expression profiles suggested that cell lines showing preference for IP growth had gene expression patterns more similar to primary tumors. We report the tumorigenicity of 17 human ovarian cancer cell lines and one mouse cell line in three distinct anatomical locations, and associated gene networks. Growth patterns and histopathology, linked to molecular characteristics, provide a valuable resource to the research community, and better guide the choice of cell lines for in vitro studies to translate efficiently into xenograft testing.