High-throughput 3D screening reveals differences in drug sensitivities between culture models of JIMT1 breast cancer cells.
High-throughput 3D screening reveals differences in drug sensitivities between culture models of JIMT1 breast cancer cells.
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DOI：
10.1371/journal.pone.0077232
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Perälä M
中科院分区：
文献类型：
--
作者：
Hongisto V;Jernström S;Fey V;Mpindi JP;Kleivi Sahlberg K;Kallioniemi O;Perälä M
体外研究癌症的传统方法是在塑料上二维单层生长永生化的癌细胞。然而，许多细胞特征在这些人工条件下受损，并且已经报道了与肿瘤相比基因表达的大变化。三维细胞培养模型已经变得越来越流行，并且由于改善了细胞与细胞的接触和类似于体内结构的结构，被认为是比二维单层更好的模型。本研究的目的是开发一种简单的高通量三维药物筛选方法，并比较药物反应在JIMT 1乳腺癌细胞生长时的二维，在聚（2-羟乙基甲基丙烯酸酯）诱导锚定独立的三维模型，并在Matrigel三维细胞培养模型。我们筛选了102种化合物，具有多个浓度和生物学重复，以观察其对细胞增殖的影响。在铺板后立即处理细胞，或者在药物处理前使其在三维培养物中生长4天。在模型之间观察到药物反应的较大变化，表明不能基于单一药物的作用来比较培养模型影响的药物敏感性。然而，我们用63种最突出的药物表明，在一般情况下，生长在Matrigel上的JIMT 1细胞对药物的敏感性明显高于生长在二维培养物中的细胞，而生长在聚（甲基丙烯酸2-羟乙酯）中的细胞的反应与二维培养物相似。此外，比较细胞培养模型与异种移植肿瘤的基因表达谱表明，在基质胶中培养的细胞和作为异种移植物的细胞彼此最相似。在这项研究中，我们还建议，三维文化可以提供一个平台，系统的实验更大的化合物集合在一个高通量的模式，并作为替代传统的二维屏幕更好的可比性，在体内状态。
The traditional method for studying cancer in vitro is to grow immortalized cancer cells in two-dimensional monolayers on plastic. However, many cellular features are impaired in these artificial conditions, and large changes in gene expression compared to tumors have been reported. Three-dimensional cell culture models have become increasingly popular and are suggested to be better models than two-dimensional monolayers due to improved cell-to-cell contact and structures that resemble in vivo architecture. The aim of this study was to develop a simple high-throughput three-dimensional drug screening method and to compare drug responses in JIMT1 breast cancer cells when grown in two dimensions, in poly(2-hydroxyethyl methacrylate) induced anchorage-independent three-dimensional models, and in Matrigel three-dimensional cell culture models. We screened 102 compounds with multiple concentrations and biological replicates for their effects on cell proliferation. The cells were either treated immediately upon plating, or they were allowed to grow in three-dimensional cultures for 4 days before the drug treatment. Large variations in drug responses were observed between the models indicating that comparisons of culture model-influenced drug sensitivities cannot be made based on the effects of a single drug. However, we show with the 63 most prominent drugs that, in general, JIMT1 cells grown on Matrigel were significantly more sensitive to drugs than cells grown in two-dimensional cultures, while the responses of cells grown in poly(2-hydroxyethyl methacrylate) resembled those of the two-dimensional cultures. Furthermore, comparing the gene expression profiles of the cell culture models to xenograft tumors indicated that cells cultured in Matrigel and as xenografts most closely resembled each other. In this study, we also suggest that three-dimensional cultures can provide a platform for systematic experimentation of larger compound collections in a high-throughput mode and be used as alternatives to traditional two-dimensional screens for better comparability to the in vivo state.
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DOI：
10.1186/bcr3329
发表时间：
2012-10-12
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Aceto N;Duss S;MacDonald G;Meyer DS;Roloff TC;Hynes NE;Bentires-Alj M
通讯作者：
Bentires-Alj M
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
6.4
作者：
DIMANCHEBOITREL, MT;PELLETIER, H;CHAUFFERT, B
通讯作者：
CHAUFFERT, B
影响因子：
2.7
作者：
Kokkinos, Maria I.;Wafai, Razan;Waltham, Mark
通讯作者：
Waltham, Mark
DOI：
10.1073/pnas.84.13.4490
发表时间：
1987-07-01
影响因子：
11.1
作者：
KUCZEK, T;AXELROD, DE
通讯作者：
AXELROD, DE