Defining new criteria for selection of cell-based intestinal models using publicly available databases.
Defining new criteria for selection of cell-based intestinal models using publicly available databases.
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DOI：
10.1186/1471-2164-13-274
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发表时间：
2012-06-22
期刊：
影响因子：
4.4
通讯作者：
Anderle P
中科院分区：
文献类型：
--
作者：
Christensen J;El-Gebali S;Natoli M;Sengstag T;Delorenzi M;Bentz S;Bouzourene H;Rumbo M;Felsani A;Siissalo S;Hirvonen J;Vila MR;Saletti P;Aguet M;Anderle P
在大量具有广泛功能特性的肠源细胞系中选择相关细胞系的标准仍然不明确。因此，本研究的目的是建立客观的标准来选择相关细胞系，以评估其作为肿瘤模型和药物吸收研究的适宜性。我们利用公开可用的表达特征和基于细胞的功能测定来描绘各种肠结肠癌细胞系和正常肠上皮之间的差异。我们将一组肠细胞系与患者来源的正常上皮和肿瘤上皮进行了比较，并根据与致癌途径活性、上皮-间质转化（EMT）和干性、迁移特性、增殖活性、转运蛋白表达谱和化学敏感性相关的特征对它们进行了分类。例如，SW480代表了emt高的迁移表型，根据患者衍生数据库，SW480在与更差的总生存期和更高的复发风险相关的特征方面得分最高。另一方面，分化后的HT29和T84细胞的基因表达模式与肿瘤大块来源细胞最接近。关于药物吸收，我们证实分化的Caco-2细胞是小肠主动吸收研究的选择模型。关于化疗敏感性，我们无法证实最近提出的化疗耐药性与EMT性状的关联。然而，通过挖掘NCI60 GI50值，发现了一个新的特征，该特征允许根据肠道细胞系对常用化疗药物的药物反应性对其进行排序。这项研究提出了一种直接的策略，利用公开可用的基因表达数据来指导基于细胞的模型的选择。虽然这种方法不能克服这种模型的主要局限性，但引入所选特征的等级顺序可能允许选择更适合和更相关的模型细胞系。
The criteria for choosing relevant cell lines among a vast panel of available intestinal-derived lines exhibiting a wide range of functional properties are still ill-defined. The objective of this study was, therefore, to establish objective criteria for choosing relevant cell lines to assess their appropriateness as tumor models as well as for drug absorption studies. We made use of publicly available expression signatures and cell based functional assays to delineate differences between various intestinal colon carcinoma cell lines and normal intestinal epithelium. We have compared a panel of intestinal cell lines with patient-derived normal and tumor epithelium and classified them according to traits relating to oncogenic pathway activity, epithelial-mesenchymal transition (EMT) and stemness, migratory properties, proliferative activity, transporter expression profiles and chemosensitivity. For example, SW480 represent an EMT-high, migratory phenotype and scored highest in terms of signatures associated to worse overall survival and higher risk of recurrence based on patient derived databases. On the other hand, differentiated HT29 and T84 cells showed gene expression patterns closest to tumor bulk derived cells. Regarding drug absorption, we confirmed that differentiated Caco-2 cells are the model of choice for active uptake studies in the small intestine. Regarding chemosensitivity we were unable to confirm a recently proposed association of chemo-resistance with EMT traits. However, a novel signature was identified through mining of NCI60 GI50 values that allowed to rank the panel of intestinal cell lines according to their drug responsiveness to commonly used chemotherapeutics. This study presents a straightforward strategy to exploit publicly available gene expression data to guide the choice of cell-based models. While this approach does not overcome the major limitations of such models, introducing a rank order of selected features may allow selecting model cell lines that are more adapted and pertinent to the addressed biological question.
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影响因子：
24.5
作者：
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通讯作者：
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影响因子：
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