Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA182210 | ENA |
REPOSITORIES: ENA
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Project description:The traditional method for studying cancer in vitro is to grow immortalized cancer cells in two-dimensional (2D) monolayers on plastic. However, many cellular features are impaired in these unnatural conditions and big alterations in gene expression in comparison to tumors have been reported. Three-dimensional (3D) cell culture models have become increasingly popular and are suggested to be better models than 2D monolayers due to improved cell-to-cell contacts and structures that resemble in vivo architecture. The aim of this study was to develop a simple high-throughput 3D drug screening method and to compare drug responses in JIMT1 breast cancer cells when grown in 2D, in polyHEMA coated anchorage independent 3D models and in Matrigel on-top 3D 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 3D for four days prior to the drug treatment. Big variations in drug responses were observed between the models indicating that comparisons of culture model influenced drug sensitivities cannot be made based on 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 2D cultures, while responses of cells grown in polyHEMA resembled those of 2D. Furthermore, comparison of 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 3D cultures can provide a platform for systematic experimentation of larger compound collections in a high-throughput mode and be used as alternatives for traditional 2D screens towards better comparability to in vivo state. Gene expression analysis of JIMT1 breast cancer cells cultured as xenografts for 43 days, in two dimensional cultures for seven days (2D7d), in polyHEMA three dimensional cell culture models for four and seven days (PH7d and PH7d), and in Matrigel three dimensional cultures for four and seven days (MG4d and MG7d). Two biological replicates was included for each sample.
2013-10-30 | E-GEOD-42529 | biostudies-arrayexpress
Project description:The traditional method for studying cancer in vitro is to grow immortalized cancer cells in two-dimensional (2D) monolayers on plastic. However, many cellular features are impaired in these unnatural conditions and big alterations in gene expression in comparison to tumors have been reported. Three-dimensional (3D) cell culture models have become increasingly popular and are suggested to be better models than 2D monolayers due to improved cell-to-cell contacts and structures that resemble in vivo architecture. The aim of this study was to develop a simple high-throughput 3D drug screening method and to compare drug responses in JIMT1 breast cancer cells when grown in 2D, in polyHEMA coated anchorage independent 3D models and in Matrigel on-top 3D 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 3D for four days prior to the drug treatment. Big variations in drug responses were observed between the models indicating that comparisons of culture model influenced drug sensitivities cannot be made based on 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 2D cultures, while responses of cells grown in polyHEMA resembled those of 2D. Furthermore, comparison of 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 3D cultures can provide a platform for systematic experimentation of larger compound collections in a high-throughput mode and be used as alternatives for traditional 2D screens towards better comparability to in vivo state.
2013-10-30 | GSE42529 | GEO
Project description:The development of high-throughput anticancer drug screening using patient-derived cancer cell lines (PDCs) that maintain their original characteristics in an in vitro three-dimensional (3D) culture system poses a significant challenge for achieving personalized cancer medicine. Because stromal tissue plays a critical role in the composition and maintenance of the cancer microenvironment, in vitro 3D-culture using reconstructed stromal tissues has attracted much attention. Here, a simple and unique in vitro 3D-culture method using heparin and collagen together with fibroblast and endothelial cells to fabricate vascularized 3D-stromal tissues for in vitro culture of PDCs is reported. While co-treatment with bevacizumab, a monoclonal antibody against the vascular endothelial growth factor, and 5-fluorouracil (5-FU) significantly reduced the survival rate of the 3D-cultured PDCs to 30%, separate addition of each drug did not induce such strong cytotoxicity, suggesting the possibility of evaluating the combined effect of anticancer drug and an angiogenesis inhibitor. Surprisingly, drug evaluation using eight PDCs with the 3D-culture method resulted in a drug efficacy concordance rate of 75% with clinical history. The model is expected to be applied to in vitro throughput drug screening for the development of personalized cancer medicine.
2023-12-01 | GSE248026 | GEO
Project description:Background: The main focus of the work was the evaluation of gene expression differences between our established NSCLC 3D cell culture model and the 2D cell culture in regard to the use of our model for drug screening applications. Methods: The non-small cell lung cancer (NSCLC) cell lines Colo699 and A549 were cultivated as monolayer (2D) on cell culture plates for five days or as microtissues (3D) in a hanging-drop system for five and ten days, respectively. Cells and microtissues were harvested and Affymetrix chip analyses were performed with the prior isolated RNA. This was repeated in three independent experiments. Subsequent biostatistical data analyses tested for reproducibility, comparability and significant differences in gene expression profiles between cell lines, experiments and culture methods. Results: The analyses revealed a high interassay correlation within the distinct culture systems, thus proving a high validity of our data. The comparison of 3D versus 2D cell cultures revealed significant differences in RNA expression (979 genes for A549; 1106 genes for Colo699), but the overlap of changes in RNA profiles between the cell lines at the individual gene level was small (149 genes), potentially reflecting overall heterogeneity and their origin, i.e. primary vs pleural effusion. Nevertheless, these RNA expression changes affected most relevant cancer-associated pathways as DNA methylation, cell cycle, rRNA expression and meiosis pathways. Furthermore, the expression differences between 2D and 3D were more evident after longer cultivation time, which supports the hypothesis of cultivation related mechanisms and the usage of long-time cultivation systems. Conclusion: In summary, our data support the need of innovative 3D drug testing systems to close the gap between in-vitro drug screening and in-vivo data. Thus, our 3D NSCLC model might provide a model to address the challenge of microenviroment associated resistance mechanisms, as well as cell-cell interaction related effects.
2018-02-07 | GSE78210 | GEO
Project description:Tumor-associated macrophage (TAM) infiltration is a characteristic of triple-negative breast cancer (TNBC) related to drug resistance and poor prognosis. Unraveling intricate cell-cell interactions in the tumor microenvironment (TME) remains challenging, especially when using a standardized 3D culture system. This study used the TNBC cell line, MDA-MB-231, and polarized M1-like or M2-like macrophages derived from THP-1 monocytes to establish 3D co-culture spheroids for mimicking the TME environment. Drug efficacy, epithelial-mesenchymal transition (EMT) in cancer cells, macrophage phenotypes, and RNA sequencing of spheroids were performed. We observed that M2 macrophages increased the viability and proliferation rate of MDA-MB-231 cells in the 3D spheroids, while both M1 and M2 macrophages increased the chemosensitivity of MDA-MB-231 cells to doxorubicin and paclitaxel. Interestingly, instead of maintaining their phenotypes, M1 and M2 macrophages lost some polarization when 3D co-cultured with MDA-MB-231 cells. Compared with 2D cultures, an expected mesenchymal transition was observed in 3D spheroid MDA-MB-231 cells. However, both M1 and M2 macrophages induced a partial epithelial reversion in co-cultured spheroids. Deconvolution of our bulk RNA sequencing results verified the existence of phenotypic transitions between M1 and M2 macrophages when co-cultured with MDA-MB-231 cells in 3D spheroids. In conclusion, our findings suggest that a 3D co-culture system of polarized macrophages and breast cancer cells can serve as an effective platform for studying the dynamic cellular phenotype changes that occur in a heterogeneous environment contributing to chemoresistance. This 3D co-culture system may provide a valuable tool for drug screening to identify targeted therapies for cancer.
2026-08-03 | GSE304137 | GEO
Project description:Quantitative high-throughput 2D drug screening (n=3436 compounds) was conducted across 12 patient-derived LGSOC cell lines representing MAPK-mutant and no-specific-molecular-profile (NSMP) subtypes, and a immortalised normal ovarian line (IOSE-523) as toxicity control. Hits were prioritised for synergy testing (29 combinations) with 6 anchor drugs and validated in 2D and 3D spheroid models. Mechanistic studies to elucidate mechanisms of drug sensitivity and resistance to drug classes was conducted via MAC-Seq transcriptomics (multiplexed analysis of cells, high-throughput RNA seq).
2026-05-27 | GSE313916 | GEO
Project description:Development of a reliable method for human triple-negative breast cancer organotypic culture: Improving imaging and genomic studies in 3D cultures The primary objectives of this study are to develop an advanced three-dimensional cell culture system to better model the tumor microenvironment in triple-negative breast cancer (TNBC), analyze the differences in molecular and cellular behavior between two-dimensional (2D) and 3D cultures, and investigate the impact of these differences on key oncogenic signaling pathways, specifically PI3K and β-catenin.
2024-09-20 | GSE277405 | GEO
Project description:The traditional method for studying cancer in vitro is to grow immortalized cancer cells in two-dimensional (2D) monolayers on plastic. However, many cellular features are impaired in these unnatural conditions and big alterations in gene expression in comparison to tumors have been reported. Three-dimensional (3D) cell culture models have become increasingly popular and are suggested to be better models than 2D monolayers due to improved cell-to-cell contacts and structures that resemble in vivo architecture. The aim of this study was to compare gene expression patterns of MCF7 breast cancer cells when grown as xenografts, in 2D, in polyHEMA coated anchorage independent 3D models and in Matrigel on-top 3D cell culture models. Surprisingly small variations in gene expression patterns were observed between the models indicating that 3D and xenograft are not always that different from 2D cell cultures. Gene expression analysis of MCF7 breast cancer cells cultured as xenografts for 43 days, in two dimensional cultures for seven days (2D7d), in polyHEMA three dimensional cell culture models for four and seven days (PH7d and PH7d), and in Matrigel three dimensional cultures for four and seven days (MG4d and MG7d). Two biological replicates was included for each sample.
2013-10-30 | E-GEOD-47583 | biostudies-arrayexpress
Project description:Complex three-dimensional (3D) in vitro model systems that recapitulate human tumor biology are essential to better understand the pathophysiology of the disease and to aid in the discovery of novel anti-cancer therapies. 3D organotypic cultures exhibit intercellula communication, nutrient and oxygen gradients, and cell polarity that is lacking in traditional two-dimensional (2D) monolayer cultures. In the present study, we could demonstrate that 2D and 3D cancer models exhibit different drug sensitivities towards both targeted inhibitors of EGFR signaling and broad acting cytotoxic agents. Changes in the kinase activities of Erb family members and differential expression of apoptosis- and survival-associated genes before and after drug treatment may account for the differential drug sensitivities. Importantly, EGFR oncoprotein addiction was evident only in the 3D cultures mirroring the effect of EGFR inhibition in the clinic. Furthermore, targeted drug efficacy was strongly increased when incorporating cancer-associated fibroblasts into the 3D cultures. Taken together, we could provide conclusive evidence that complex 3D cultures are more predictive of the clinical outcome than their 2D counterparts. In the future, 3D cultures will be instrumental for understanding the mode of action of drugs, identifying genotype-drug response relationships and developing patient-specific and personalized cancer treatments.
2017-11-30 | GSE102722 | GEO
Project description:Rare cancers comprise over 200 distinct types accounting for 20–25% of U.S. cancer diagnoses yet receive limited therapeutic investment due to small patient populations and resource constraints. Drug repurposing offers a viable strategy, and large-animal models such as minipigs provide physiologically realistic platforms for preclinical evaluation. However, scalable systems for systematically screening large drug libraries in rare cancer models remain unavailable. We developed an integrated pipeline combining a minipig spinal cord glioma (SCG) model with miniaturized ultra-high-throughput screening (uHTS). Primary SCG cells were cultured in 3D platforms for rapid screening of bioactive compounds. Lead candidates underwent validation through 3D spheroid assays, in vivo xenografting, RNA sequencing, immunohistochemistry, and histological analysis. Human SCG tissue samples and population-level datasets assessed translational relevance. uHTS screening identified Clofoctol as a lead compound with potent glioma growth inhibition in both primary SCG cells and xenograft models. Mechanistic studies revealed pleiotrophin (PTN) as a key target, with confirmatory expression patterns in human SCG samples, establishing translational validity. Integration of large-animal cancer models with drug-repurposing pipelines and uHTS platforms is feasible and effective for rare cancer drug discovery. This approach successfully identified Clofoctol, an FDA-approved compound with therapeutic potential for spinal cord gliomas and establishes a scalable model applicable to other orphan cancers.
2026-06-20 | GSE335535 | GEO