Generation of a Three-Dimensional In Vitro Ovarian Cancer Co-culture Model for Drug Screening Assays
Abstract
In vitro 3D culture models have emerged in the cancer field due to their ability to recapitulate characteristics of the in vivo tumor. Herein, we described the establishment and characterization of 3D multicellular spheroids using ovarian cancer cells (SKOV-3) in co-culture with mesenchymal cells (MUC-9) or fibroblasts (CCD27-Sk). We demonstrated that SKOV-3 cells in co-culture were able to form regular and compact spheroids with diameters ranging from 300 to 400 µm and with a roundness close to 1.0 regardless of the type of stromal cell used. In the 3D culture an increase was not observed in spheroid diameter nor was there significant cell growth. What is more, the 3D co-cultures presented an up regulation of genes related to tumorigenesis, angiogenesis and metastases (MMP2, VEGFA, SNAI1, ZEB1 and VIM) when compared with 2D and 3D monoculture. As expected, both 3D cultures (mono and co-cultures) exhibited a higher Paclitaxel chemoresistance when compared to 2D condition. Although we did not observe differences in the Paclitaxel resistance between the 3D mono and co-cultures, the gene expression results indicate that the presence of mesenchymal cells and fibroblasts better recapitulate the in vivo tumor microenvironment, being able, therefore, to more accurately evaluate drug efficacy for ovarian cancer therapy.
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In 3D multicellular spheroid cultures, addition of fibroblasts, mesenchymal stem cells, or endothelial cells enhances spheroid size, chemoresistance and a stem-like phenotype compared to 3D monocultures.
“In 3D multicellular spheroid cultures, addition of fibroblasts, mesenchymal stem cells, or endothelial cells have been shown to enhance spheroid size, chemoresistance and a stem-like phenotype compared to 3D monocultures (Hedegaard et al., 2020; Tofani et al., 2021).”
From Three-dimensional modelling of ovarian cancer: from cell lines to organoids for discovery and personalized medicine (2022) · cites this paper as Tofani et al., 2021
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- Authors
- Tofani, L. B., Sousa, L. O., Luiz, M. T., Abriata, J. P., Marchetti, J. M., Leopoldino, A. M., & Swiech, K.
- Affiliations
- Universidade de São Paulo (BR)
- Corresponding author
- Swiech, Kamilla
- ORCID
- Venue
- Journal of Pharmaceutical Sciences
- Publisher
- Elsevier BV
- Published
- 2021-07
- Volume
- 110
- Issue
- 7
- Pages
- 2629-2636
- ISSN
- 0022-3549 (ISSN-L)
- OpenAlex
- W3155774046
- Cited by
- 14
- References
- 59
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 4 · 2023: 4 · 2022: 3 · 2021: 1
- FWCI
- 1.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pharmaceutical Sciences (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Coordination of Higher Education Personnel Improvement
- Universidade de São Paulo
- Conselho Nacional de Desenvolvimento Científico e Tecnológico (443981/2014-0)
- 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, multicellular spheroids, co-culture model, tumor microenvironment, mesenchymal cells, fibroblasts, SKOV3 cells, paclitaxel resistance, drug screening, angiogenesis-related genes, metastasis-associated genes, MMP-2, VEGF-A, epithelial-mesenchymal transition
- MeSH terms
- Drug Evaluation, Preclinical, Female, Humans, Ovarian Neoplasms, Spheroids, Cellular, Coculture Techniques, Cell Line, Tumor, Early Detection of Cancer, Tumor Microenvironment
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