High-throughput 3-dimensional Culture of Epithelial Ovarian Cancer Cells as Preclinical Model of Disease
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// Victoria Heredia-Soto 1, 2 , Andrés Redondo 3, 4, 5 , Alberto Berjón 1, 6 , María Miguel-Martín 1 , Esther Díaz 4 , Roberto Crespo 4 , Alicia Hernández 7 , Laura Yébenes 1, 6 , Alejandro Gallego 3 , Jaime Feliu 2, 3, 4, 5, 8 , David Hardisson 1, 5, 6, 9 and Marta Mendiola 1, 2, 9 1 Molecular Pathology and Therapeutic Targets Research Lab, Instituto de Investigación del Hospital Universitario La Paz, IdiPAZ, Hospital Universitario La Paz, HULP, Madrid 28046, Spain 2 Centro de Investigación Biomédica en Red de Cáncer, CIBERONC. Instituto de Salud Carlos III, Madrid 28029, Spain 3 Department of Medical Oncology, Hospital Universitario La Paz, HULP, Madrid 28046, Spain 4 Translational Oncology Research Lab, IdiPAZ, Hospital Universitario La Paz, HULP, Madrid 28046, Spain 5 School of Medicine, Universidad Autónoma de Madrid, UAM, Madrid 28029, Spain 6 Department of Pathology, Hospital Universitario La Paz, HULP, Madrid 28046, Spain 7 Department of Gynecology and Obstetrics, Hospital Universitario La Paz, HULP, Madrid 28046, Spain 8 Cátedra UAM-AMGEN, Universidad Autónoma de Madrid, Campus de Cantoblanco, Madrid 28049, Spain 9 Molecular Pathology Section, Instituto de Genética Molecular y Médica, INGEMM, Hospital Universitario La Paz, HULP, Madrid 28046, Spain Correspondence to: Marta Mendiola, email: marta.mendiola@idipaz.es David Hardisson, email: david.hardisson@salud.madrid.org Keywords: ovarian cancer; epithelial mesenchymal transition; 3D cell culture model Received: August 18, 2017 Accepted: March 19, 2018 Published: April 24, 2018 ABSTRACT Background: Recent reports have identified distinct genomic patterns in ovarian carcinoma, including proliferative and mesenchymal-like groups, with worse outcome. The exact mechanisms driving the onset and progression of these tumors are still poorly understood. Additionally, researchers are concerned about the correct subtype stratification of the available cell line models, and the exploration of alternatives to monolayer culture. Identification of biomarkers to stratify cell lines, characterization of important processes as epithelial-mesenchymal transition (EMT), and the use of three-dimensional (3D) cultures as alternative models could be useful for cell line classification. Methods and Results: In this work, we present a descriptive analysis of 16 commonly used ovarian cancer cell lines. We have studied their morphology in 2- and 3D culture, and their response to cisplatin, observing in the majority of them an increased resistance in 3D. We have also performed an immunohistochemical analysis for proliferation marker Ki-67, and EMT related markers to establish phenotypes. Epithelial cells tend to show higher proliferative rates, and mesenchymal cells show an increase in EMT related markers, especially when cultured in 3D conditions. Conclusions: We have stated the complex heterogeneity of ovarian cancer models, resembling primary tumors, agreeing with the argument that the cell line model for in vitro experiments must be carefully chosen. Our results also support that tridimensional culture could be a very helpful alternative in ovarian cancer research. Regarding EMT, a very important process for the development of this disease, some related biomarkers might be further characterized for their role in this disease development.
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Formation of single large spheroids (>500 μm diameter) enables the formation of a hypoxic core, and drug, oxygen and metabolite gradients that mimic solid tumor physiology.
“Formation of single large spheroids (>500 μm diameter) enables the formation of a hypoxic core, and drug, oxygen and metabolite gradients that mimic solid tumor physiology (Vinci et al., 2012; Heredia-Soto et al., 2018).”
From Three-dimensional modelling of ovarian cancer: from cell lines to organoids for discovery and personalized medicine (2022) · cites this paper as Heredia-Soto et al., 2018
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- Authors
- Heredia-Soto, V., Redondo, A., Berjón, A., Miguel-Martín, M., Díaz, E., Crespo, R., Hernández, A., Yébenes, L., Gallego, A., Feliu, J., Hardisson, D., & Mendiola, M.
- Affiliations
- Hospital Universitario La Paz (ES)
- Centro de Investigación Biomédica en Red de Cáncer, CIBERONC. Instituto de Salud Carlos III, Madrid 28029, Spain
- ORCID
- Venue
- Oncotarget
- Publisher
- Impact Journals, LLC
- Published
- 2018-04-24
- Volume
- 9
- Issue
- 31
- Pages
- 21893-21903
- ISSN
- 1949-2553 (ISSN-L)
- PMC
- PMC5955171
- OpenAlex
- W2801664145
- Cited by
- 33
- References
- 45
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 4 · 2023: 2 · 2022: 10 · 2021: 2 · 2020: 9
- FWCI
- 2.95
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by
- Locations
- Oncotarget (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- Hispana (submittedVersion)
- Biblos-e Archivo (Universidad Autónoma de Madrid) (submittedVersion, public-domain)
- Funders
- Fundación Mutua Madrileña
- Centro de Investigación Biomédica en Red de Cáncer
- Instituto de Salud Carlos III (PNI-D+i 2008–2011, 2008-2011)
- European Regional Development Fund
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- epithelial ovarian cancer, 3D cell culture, preclinical models, epithelial-mesenchymal transition, tumor microenvironment, cancer stem cells, tumor spheroids, drug screening, drug resistance, chemoresistance, drug repurposing
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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