Cited by 33Cancer Cells and MetastasisOvarian cancer diagnosis and treatment3D Printing in Biomedical Research

A High-Throughput Screening Model of the Tumor Microenvironment for Ovarian Cancer Cell Growth

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Lal-Nag, Madhu, McGee, Lauren, Guha, Rajarshi, Lengyel, Ernst, Kenny, Hilary A., Ferrer, Marc·2017·SLAS Discovery

Abstract

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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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)
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
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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