A High-Throughput Screening Model of the Tumor Microenvironment for Ovarian Cancer Cell Growth
Open accessAbstract
The tumor microenvironment plays an important role in the processes of tumor growth, metastasis, and drug resistance. We have used a multilayered 3D primary cell culture model that reproduces the human ovarian cancer metastatic microenvironment to study the effect of the microenvironment on the pharmacological responses of different classes of drugs on cancer cell proliferation. A collection of oncology drugs was screened to identify compounds that inhibited the proliferation of ovarian cancer cells growing as monolayers or forming spheroids, on plastic and on a 3D microenvironment culture model of the omentum metastatic site, and also cells already in preformed spheroids. Target-based analysis of the pharmacological responses revealed that several classes of targets were more efficacious in cancer cells growing in the absence of the metastatic microenvironment, and other target classes were less efficacious in cancer cells in preformed spheres compared to forming spheroid cultures. These findings show that both the cellular context of the tumor microenvironment and cell adhesion mode have an essential role in cancer cell drug resistance. Therefore, it is important to perform screens for new drugs using model systems that more faithfully recapitulate the tissue composition at the site of tumor growth and metastasis.
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The organotypic mesothelial model has been adapted for high throughput drug screening of potential inhibitors of adhesion and invasion.
“This model has also been adapted for high throughput drug screening of potential inhibitors of adhesion and invasion.”
From Three-dimensional modelling of ovarian cancer: from cell lines to organoids for discovery and personalized medicine (2022) · cites this paper as Lal-Nag et al., 2017
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- Authors
- Lal-Nag, M., McGee, L., Guha, R., Lengyel, E., Kenny, H. A., & Ferrer, M.
- Affiliations
- National Institutes of Health (US)
- University of Chicago (US)
- Corresponding author
- Ferrer, Marc
- Venue
- SLAS Discovery
- Publisher
- Elsevier BV
- Published
- 2017-06
- Volume
- 22
- Issue
- 5
- Pages
- 494-506
- ISSN
- 2472-5552 (ISSN-L)
- PMC
- PMC5815521
- OpenAlex
- W2600882249
- Cited by
- 33
- References
- 38
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 3 · 2022: 6 · 2021: 3 · 2020: 4 · 2019: 5 · 2018: 6 · 2017: 1
- FWCI
- 1.93
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- SLAS DISCOVERY (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH Intramural Research Program
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Keywords
- ovarian cancer, tumor microenvironment, 3D cell culture models, cancer cell spheroids, omental metastasis, drug resistance, high-throughput screening, tumor cell proliferation, cell adhesion, pharmacological response, metastatic microenvironment
- MeSH terms
- Antineoplastic Agents, Cell Adhesion, Female, Humans, Ovarian Neoplasms, Spheroids, Cellular, Cell Culture Techniques, Drug Resistance, Neoplasm, Cell Line, Tumor, Cell Proliferation, High-Throughput Screening Assays, Tumor Microenvironment
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