Translation of a Tumor Microenvironment Mimicking 3D Tumor Growth Co-culture Assay Platform to High-Content Screening

Krausz, Eberhard; Hoogt, Ronald de; Gustin, Emmanuel; Cornelissen, Frans W.; Grand-Perret, Thierry; Janssen, Lut; Vloemans, Nele; Wuyts, D.; Frans, Sandy; Axel, Amy; Peeters, Pieter J.; Hall, Brett M.; Cik, Miroslav

doi:10.1177/1087057112456874

Cited by 59 publications

(51 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Krausz et al [72] recently published anchorage-dependent 3D cell culture assay methodology for prostate cancer, which is suitable for high-content screening (HCS) (96-well microtitre plate format). Initially, comparisons of various imaging platforms (MIAS-2 ® , IN Cell Analyzer 2000 ® and an Opera ® ) and their respective analysis programs along with their in house tool, Plate-based High-Content Analysis Evaluation and Dynamic Reliability Assurance (Phaedra) were performed.…”

Section: Utilizing 3d Tumor Models In Drug Discovery: Progress So Farmentioning

confidence: 99%

“…Several of these programs consist of features which enable batch analysis of large data sets that are becoming readily accessible for most academic groups, and are relatively user friendly. In addition, various analysis protocols which focus on deconstructing elements of cells cultured in 3D, such as morphological profiles and biomarkers, designed for low-throughput and HCS experiments have been developed and published [72,81,82]. Technological advances such as these may not only allow a broader scope of models to be developed, but may further encourage the incorporation of 3D models in the search for anti-cancer drug candidates in the drug discovery pipeline.…”

Section: Towards More Complex Assays Suitable For Integration In Dmentioning

confidence: 99%

“…3D cancer co-culture models have been developed in both low-throughput [89,90,91,92] and high-throughput [5,72,73] formats. However, at the present time, only cancer cells along with one other cell type (e.g., fibroblasts) have been incorporated into models suitable in screening new compounds in a high-throughput manner.…”

Section: Towards More Complex Assays Suitable For Integration In Dmentioning

confidence: 99%

See 2 more Smart Citations

Advanced Cell Culture Techniques for Cancer Drug Discovery

Lovitt

Shelper

Avery

2014

Biology

223

218

View full text Add to dashboard Cite

Human cancer cell lines are an integral part of drug discovery practices. However, modeling the complexity of cancer utilizing these cell lines on standard plastic substrata, does not accurately represent the tumor microenvironment. Research into developing advanced tumor cell culture models in a three-dimensional (3D) architecture that more prescisely characterizes the disease state have been undertaken by a number of laboratories around the world. These 3D cell culture models are particularly beneficial for investigating mechanistic processes and drug resistance in tumor cells. In addition, a range of molecular mechanisms deconstructed by studying cancer cells in 3D models suggest that tumor cells cultured in two-dimensional monolayer conditions do not respond to cancer therapeutics/compounds in a similar manner. Recent studies have demonstrated the potential of utilizing 3D cell culture models in drug discovery programs; however, it is evident that further research is required for the development of more complex models that incorporate the majority of the cellular and physical properties of a tumor.

show abstract

Section: Utilizing 3d Tumor Models In Drug Discovery: Progress So Farmentioning

confidence: 99%

Section: Towards More Complex Assays Suitable For Integration In Dmentioning

confidence: 99%

Section: Towards More Complex Assays Suitable For Integration In Dmentioning

confidence: 99%

See 1 more Smart Citation

Advanced Cell Culture Techniques for Cancer Drug Discovery

Lovitt

Shelper

Avery

2014

Biology

223

218

View full text Add to dashboard Cite

show abstract

“…This was achieved by development of the 3-Dimensional Tumor Growth Assay (3D-TGA; refs. 25,26), which utilizes a low stiffness laminin-rich extracellular matrix (ECM; ref. 27) to embed tumor cells and admixing with stromal cells to provide the paracrine signaling present in the TME of solid tumors (13,14).…”

Section: Introductionmentioning

confidence: 99%

3-Dimensional Patient-Derived Lung Cancer Assays Reveal Resistance to Standards-of-Care Promoted by Stromal Cells but Sensitivity to Histone Deacetylase Inhibitors

Onion

Argent

Reece-Smith

et al. 2016

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

There is a growing recognition that current preclinical models do not reflect the tumor microenvironment in cellular, biological, and biophysical content and this may have a profound effect on drug efficacy testing, especially in the era of molecular-targeted agents. Here, we describe a method to directly embed low-passage patient tumor-derived tissue into basement membrane extract, ensuring a low proportion of cell death to anoikis and growth complementation by coculture with patient-derived cancer-associated fibroblasts (CAF). A range of solid tumors proved amenable to growth and pharmacologic testing in this 3D assay. A study of 30 early-stage non-small cell lung cancer (NSCLC) specimens revealed high levels of de novo resistance to a large range of standard-of-care agents, while histone deacetylase (HDAC) inhibitors and their combination with antineoplastic drugs displayed high levels of efficacy. Increased resistance was seen in the presence of patient-derived CAFs for many agents, highlighting the utility of the assay for tumor microenvironment-educated drug testing. Standard-of-care agents showed similar responses in the 3D ex vivo and patient-matched in vivo models validating the 3D-Tumor Growth Assay (3D-TGA) as a high-throughput screen for close-to-patient tumors using significantly reduced animal numbers. Mol Cancer Ther; 15(4); 753-63. Ó2016 AACR.

show abstract

“…An interesting study by Krausz et al described an anchorage-dependent 3D co-culture model including tumor cells and stromal cells organized in a complex ECM microenvironment [46]. This model was used to assess tumor growth and focused on non-uniform 3D-colony structures as opposed to uniform single MCTS.…”

Section: Progress Towards 3d Hti and Hcs Drug Discoverymentioning

confidence: 99%

High-throughput imaging: Focusing in on drug discovery in 3D

Zhou

Voss

et al. 2016

Methods

View full text Add to dashboard Cite

3D organotypic culture models such as organoids and multicellular tumor spheroids (MCTS) are becoming more widely used for drug discovery and toxicology screening. As a result, 3D culture technologies adapted for high-throughput screening formats are prevalent. While a multitude of assays have been reported and validated for high-throughput imaging (HTI) and high-content screening (HCS) for novel drug discovery and toxicology, limited HTI/HCS with large compound libraries have been reported. Nonetheless, 3D HTI instrumentation technology is advancing and this technology is now on the verge of allowing for 3D HCS of thousands of samples. This review focuses on the state-of-the-art high-throughput imaging systems, including hardware and software, and recent literature examples of 3D organotypic culture models employing this technology for drug discovery and toxicology screening.

show abstract

Translation of a Tumor Microenvironment Mimicking 3D Tumor Growth Co-culture Assay Platform to High-Content Screening

Cited by 59 publications

References 25 publications

Advanced Cell Culture Techniques for Cancer Drug Discovery

Advanced Cell Culture Techniques for Cancer Drug Discovery

3-Dimensional Patient-Derived Lung Cancer Assays Reveal Resistance to Standards-of-Care Promoted by Stromal Cells but Sensitivity to Histone Deacetylase Inhibitors

High-throughput imaging: Focusing in on drug discovery in 3D

Contact Info

Product

Resources

About