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Ovarian Cancer Cell Line Panel (OCCP): Clinical Importance of In Vitro Morphological Subtypes
Open accessAbstract
Epithelial ovarian cancer is a highly heterogeneous disease and remains the most lethal gynaecological malignancy in the Western world. Therapeutic approaches need to account for inter-patient and intra-tumoural heterogeneity and detailed characterization of in vitro models representing the different histological and molecular ovarian cancer subtypes is critical to enable reliable preclinical testing. There are approximately 100 publicly available ovarian cancer cell lines but their cellular and molecular characteristics are largely undescribed. We have characterized 39 ovarian cancer cell lines under uniform conditions for growth characteristics, mRNA/microRNA expression, exon sequencing, drug response for clinically-relevant therapeutics and collated all available information on the original clinical features and site of origin. We tested for statistical associations between the cellular and molecular features of the lines and clinical features. Of the 39 ovarian cancer cell lines, 14 were assigned as high-grade serous, four serous-type, one low-grade serous and 20 non-serous type. Three morphological subtypes: Epithelial (n = 21), Round (n = 7) and Spindle (n = 12) were identified that showed distinct biological and molecular characteristics, including overexpression of cell movement and migration-associated genes in the Spindle subtype. Comparison with the original clinical data showed association of the spindle-like tumours with metastasis, advanced stage, suboptimal debulking and poor prognosis. In addition, the expression profiles of Spindle, Round and Epithelial morphologies clustered with the previously described C1-stromal, C5-mesenchymal and C4 ovarian subtype expression profiles respectively. Comprehensive profiling of 39 ovarian cancer cell lines under controlled, uniform conditions demonstrates clinically relevant cellular and genomic characteristics. This data provides a rational basis for selecting models to develop specific treatment approaches for histological and molecular subtypes of ovarian cancer.
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“Still, often phenotypes such as drug response observed in vitro have been unable to mirror in vivo models, likely due to factors missing in the tumor microenvironment that are absent from homogeneous cell lines cultures such as stromal and immune cells (Beaufort et al., 2014).”
From Three-dimensional modelling of ovarian cancer: from cell lines to organoids for discovery and personalized medicine (2022) · cites this paper as Beaufort et al., 2014
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BackgroundMethodInfluential
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Fiegl, H., Hagenbuchner, J., Kyvelidou, C., Seeber, B., Sopper, S., Tsibulak, I., Wieser, V. E., Reiser, E., Roessler, J., Huhtinen, K., et al. (2022) · Gynecologic Oncology · doi:10.1016/j.ygyno.2022.01.008 · Cited by 5
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Cyclic Peptides Acting as Allosteric Inhibitors of Human Thymidylate Synthase and Cancer Cell Growth
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MethodEfficacy of a Covalent Microtubule Stabilizer in Taxane-Resistant Ovarian Cancer Models
Yee, S. S., & Risinger, A. L. (2021) · Molecules · doi:10.3390/molecules26134077 · Cited by 5
“While the OVCAR-8 cell line used above is characterized as HGSOC, we wanted to further evaluate the potency and efficacy of taccalonolide AF in a broader panel of molecularly diverse HGSOC cell lines [38].”
InfluentialBarnes, B. M., Nelson, L., Tighe, A., Morgan, R. D., McGrail, J. C., & Taylor, S. S. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.07.14.202457 · Cited by 5
“The EOC subtype from which commonly used ovarian cancer cell lines were derived has remained a controversial topic for many years (Anglesio et al., 2013; Beaufort et al., 2014; Coscia et al., 2016; Domcke et al., 2013).”
BackgroundStaff, T. P. O. (2015) · PLoS ONE · doi:10.1371/journal.pone.0122284 · Cited by 5
Chung, C., Yueh, B., Subhash, S., Eskiocak, O., Nizam, A., Viola, M. G., Belleau, P., Kredentser, A., Kapedani, A., Krasnitz, A., et al. (2026) · Cancer Research Communications · doi:10.1158/2767-9764.crc-25-0193 · Cited by 4
“A few long-established cell lines have been used for characterization and mechanistic studies (19) but, these cell lines do not fully recapitulate patient-specific clinical and molecular characteristics of the disease.”
Pozzi, C., Santucci, M., Marverti, G., D’Arca, D., Tagliazucchi, L., Ferrari, S., Gozzi, G., Losi, L., Tassone, G., Mangani, S., et al. (2021) · Cancers · doi:10.3390/cancers13092061 · Cited by 4
“The difference may derive from their different expression of the enzymes of the folate cycle and nucleotide metabolism, which was shown to affect the cellular response to another antifolate, pemetrexed [23,51].”
BackgroundA Novel Role of Connective Tissue Growth Factor in the Regulation of the Epithelial Phenotype
Gogoi, R. P., Galoforo, S., Fox, A. L., Morris, C., Ramos, H., Gogoi, V., Chehade, H., Adzibolosu, N. K., Shi, C., Zhang, J., et al. (2023) · Cancers · doi:10.3390/cancers15194834 · Cited by 5
“, OVCA433, SKOv3, and A2780 have mesenchymal characteristics [28,29].”
BackgroundEstablishment and characterization of a novel ovarian high-grade serous carcinoma cell line—IPO43
SILVA, F. A. B. N. D., Coelho, F., Peixoto, A., Pinto, P., Martins, C., Frombach, A.-S., Santo, V. E., Brito, C., Guimarães, A., & Félix, A. (2022) · Cancer Cell International · doi:10.1186/s12935-022-02600-3 · Cited by 4
“These is similar to the previous two cell lines described [3].”
BackgroundResultInfluentialMicroRNA regulation of RAD51 in serous ovarian cancer modulates chemotherapy response
Wiemer, E. A. C., & Berns, E. M. J. J. (2015) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djv161 · Cited by 4
Mohl, D. A., Lagies, S., Lonzer, A., Pfäffle, S. P., Gross, P., Benka, M., Jäger, M., Huber, M. C., Günther, S., Plattner, D. A., et al. (2025) · Cells · doi:10.3390/cells14090626 · Cited by 4
Žymantaitė, E., Gabrielaitė, M., Pašukonienė, V., & Mlynska, A. (2025) · Disease Models & Mechanisms · doi:10.1242/dmm.052451 · Cited by 3
“ESA expression remained stable within each strain across P25 to P50 (Fig.”
InfluentialCurrent Developments of CAR-T and CAR-NK Cell Therapies for Ovarian Cancer
Azani, A., Hasani, S., Sharafi, M., Gharedaghi, H., Doachi, R., Ahangari, F., Asadi, F., Ghasrsaz, H., Foroozand, H., Baradaran, M., et al. (2025) · Stem Cell Reviews and Reports · doi:10.1007/s12015-025-11024-1 · Cited by 4
“Ovarian cancer (OC) is recognized as the most lethal gyne-cological malignancy, primarily due to late-stage diagnosis and tumor heterogeneity, which complicates treatment and reduces survival rates [1].”
Valenzuela, M., Varas, A., Rubilar-Huenchuman, M., Lorca, M., Mella, J., Espinosa‐Bustos, C., Mellado, M., & Echeverría, J. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1746658 · Cited by 3
“High-grade serous ovarian cancer (HGSOC), which accounts for approximately 70% of cases, exhibits substantial genomic instability and distinct chemoresistance mechanisms, features typically modeled in lines such as SKOV-3 or OVCAR-3 (Domcke et al., 2013; Beaufort et al., 2014).”
Shalev, N., Kendall, M., Kumar, N., Tiwari, S., Anil, S. M., Hauschner, H., Swamy, S. G., Doron-Faingenboim, A., Belausov, E., Kendall, B. E., et al. (2024) · Frontiers in Genetics · doi:10.3389/fgene.2024.1333964 · Cited by 3
The selenoenzyme type I iodothyronine deiodinase: a new tumor suppressor in ovarian cancer
Alfandari, A., Moskovich, D., Weisz, A., Katzav, A., Kidron, D., Beiner, M. E., Josephy, D., Asali, A., Hants, Y., Yagur, Y., et al. (2024) · Molecular Oncology · doi:10.1002/1878-0261.13612 · Cited by 3
“The basal levels of DIO1 were analyzed in HGSOC cells (ES-2 and Kuramochi), which were shown to correlate with the genomic profiling of ovarian cancer patients [20,21].”
BackgroundBülbül, M. V., Mermer, A., Kolbaşı, B., Kocabaş, F., Kalender, S. M., Aydın, A. K., Demircan, T., & Keskin, İ. (2024) · Pharmaceuticals · doi:10.3390/ph17121562 · Cited by 3
Perez-Juarez, C. E., Arechavaleta-Velasco, F., Méndez, C., & Dı́az-Cueto, L. (2020) · Medical Oncology · doi:10.1007/s12032-020-01383-9 · Cited by 3
Antitumoral Effect of Plocabulin in High Grade Serous Ovarian Carcinoma Cell Line Models
Heredia-Soto, V., Escudero, J., Miguel, M. P. D., Ruiz, P., Gallego, A., Berjón, A., Hernández, A., Martínez, M., Zheng, S., Tang, J. P., et al. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.862321 · Cited by 3
“PEO1 and PEO16 harbor reported deleterious mutations in BRCA2 (16).”
BackgroundGentian Violet Inhibits Cell Proliferation through Induction of Apoptosis in Ovarian Cancer Cells
Choi, M. S., Kim, J. H., Lee, C. Y., Lee, Y. M., Lee, S., Chang, H. K., Kim, H. J., & Heo, K. (2023) · Biomedicines · doi:10.3390/biomedicines11061657 · Cited by 3
“OVCAR8 and SKOV3 are cell lines of serous OC, and A2780 is a cell line of endometrial OC [22,23].”
BackgroundPGRMC1 and PAQR4 are promising molecular targets for a rare subtype of ovarian cancer
Kozłowska-Tomczyk, K., Borski, N., Głód, P., Gogola-Mruk, J., & Ptak, A. (2024) · Open Life Sciences · doi:10.1515/biol-2022-0982 · Cited by 3
“…line (European Collection of Authenticated Cell Cultures [ECACC]; Sigma-Aldrich, St. Louis, MO, USA Catalog No. 91091004, which is a representative clear cell cancer or LGS [10,11]); the human granulosa cell tumour-derived cell line KGN (RBRC-RCB1154, Riken Cell Bank, Ibaraki, Japan; Catalog No.”
BackgroundResultInfluentialBerkel, Ç., Keskin, A., & Çaçan, E. (2025) · Pathology - Research and Practice · doi:10.1016/j.prp.2025.155911 · Cited by 3
Ovarian Cancer Research in the Post Genomic Era — Challenges and Opportunities
Goyeneche, A. A., & Telleria, C. M. (2016) · InTech eBooks · doi:10.5772/60600 · Cited by 3
“The cell lines currently characterized as likely representing HGSOC [36-38] were developed in the 1970s and 1980s and have been poorly described.”
BackgroundSu, D., Nie, M., & Yue, J. (2021) · Annals of Translational Medicine · doi:10.21037/atm-21-583 · Cited by 3
“A2780 cells lack endogenous TP53 expression (6).”
Adams, K. M., Wendt, J.-R., Wood, J., Olson, S. L., Moreno, R., Jin, Z., Gopalan, S., & Lang, J. D. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.07.26.605381 · Cited by 3
Mechanisms of Regulation of the Expression of miRNAs and lncRNAs by Metformin in Ovarian Cancer
Alfaro, I., Vega, M., Romero, C., & Garrido, M. P. (2023) · Pharmaceuticals · doi:10.3390/ph16111515 · Cited by 2
“Studies conducted in the A2780 EOC cell line, which harbors wild-type p53 [57], have shown that metformin increases p53 protein levels [58] and that doxorubicin (a p53 activator) treatment causes upregulation of miR-145 levels [59].”
BackgroundAnticancer Effects of BRD4 Inhibitor in Epithelial Ovarian Cancer
Kim, Y., Park, W., Suh, D.-H., Kim, K., No, J. H., & Kim, Y. B. (2024) · Cancers · doi:10.3390/cancers16050959 · Cited by 2
“The recent doubts raised about the histological derivation of SKOV3 cells pose difficulties in extending the conclusions of this study [37].”
ResultThe Role of SMAD7 in the Epigenetic Regulation of TGF‐β Targets in the Metastasis of Ovarian Cancer
Chen, L., Yang, S., Chou, J., Chou, H., Yeh, C.-C., Chiu, C., Lai, H., Chan, M. W. Y., & Jhang, J. (2024) · Molecular Carcinogenesis · doi:10.1002/mc.23843 · Cited by 2
Marolt, N., Potter, B. V. L., & Rižner, T. L. (2025) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2025.118278 · Cited by 2
Skipper, T. S., Dickson, K.-A., Denes, C. E., Waller, M. A., D'Araujo, T. Y., Neely, G. G., Bowden, N. A., Faiz, A., & Marsh, D. J. (2025) · Cellular Oncology · doi:10.1007/s13402-025-01102-4 · Cited by 2
“The absence of TP53 mutation, and presence of mutations in ARID1A and mutations and amplifications in PIK3CA , which are more strongly associated with other his-totypes such as OCCC and EnOC, suggested that these cell lines be re-classified [ 79].”
Girolamo, M. D., Ibello, E., Improda, T., Tedesco, I., Dell’Aversana, C., Buonaiuto, S., Arbucci, S., D’Aniello, C., Cesare, D. D., Franco, R., et al. (2026) · Molecular Cancer · doi:10.1186/s12943-026-02630-9 · Cited by 2
“OC tumors are highly heterogeneous in morphology, consisting of three different cell types: epithelial, spindle and large/round cells [25].”
Platinum-resistance and AKT Over-expression in Ovarian Cancer
Hahne, J. C. (2015) · International Journal of Gynecology & Clinical Practices · doi:10.15344/2394-4986/2015/110 · Cited by 2
“Today approximately 100 ovarian cancer cell lines are publicly available [93].”
BackgroundIdentification of a new bisindolinone arresting IGROV1 cells proliferation
Morigi, R., Zalambani, C., Farruggia, G., Verardi, L., Esposito, D., Leoni, A., Borsetti, F., Voltattorni, M., Zambonin, L., Pincigher, L., et al. (2024) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2024.116365 · Cited by 2
“TP53, BRCA1 and BRCA2 genes are mutated, but BRCA2 mutation is silent; in total there are three mutated genes in homologous recombination repair pathway [15,16].”
A Cell Line–based Immunohistochemical p53 Expression Pattern Control Panel
Hussain, I., Howard, R. S., Syed, V., Allgäuer, M., Gong, H., Xing, D., & Andersen, J. D. (2018) · International Journal of Gynecological Pathology · doi:10.1097/pgp.0000000000000537 · Cited by 2
Wang, F., Chang, J. T.-H., Zhang, Z., Morrison, G., Nath, A., Bhutra, S., & Huang, R. S. (2017) · Oncotarget · doi:10.18632/oncotarget.22870 · Cited by 2
“In addition, high throughput drug screening has been conducted in large variety of cancer cell lines [9-11].”
BackgroundGemperle, J., Harrison, T. S., Flett, C., Adamson, A. D., & Caswell, P. T. (2022) · eLife · doi:10.7554/elife.76651 · Cited by 2
Ao, W., Kim, H. I., Tommarello, D., Conrads, K. A., Hood, B. L., Litzi, T. A., Abulez, T. S., Teng, P.-N., Dalgard, C. L., Zhang, X., et al. (2023) · Gynecologic Oncology · doi:10.1016/j.ygyno.2023.08.004 · Cited by 2
Models of High-Grade Serous Ovarian CarcinomaPreprint
Pundel, O. J., & Neel, B. G. (2025) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a041949 · Cited by 2
Assessment of Antitumor Activity of Vinca herbacea on Human Ovarian Cancer Cell Line
Dehghanipour, S., Saadatmand, S., Roodbari, N. H., & Mahdavi, M. (2021) · Immunoregulation · doi:10.32598/immunoregulation.3.2.6 · Cited by 1
“It is well known that the inhibition of MMPs prevents tumor invasion and metastasis [29, 48, 49].”
BackgroundExploring miRNA profile associated with cisplatin resistance in ovarian cancer cells
Alghamian, Y., Soukkarieh, C., Aljapawe, A., & Murad, H. (2024) · Biochemistry and Biophysics Reports · doi:10.1016/j.bbrep.2024.101906 · Cited by 1
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“Additionally, SKOV3 was chosen for LOXL2 knockdown due to its prevalence in ovarian cancer research despite its divergence from the HGSOC phenotype [29, 30] (Fig.”
Phosphodiesterase 7: a potential novel therapeutic target in ovarian cancer
Tessarollo, N. G., Guimarães, I. D. S., dos Santos, D. Z., Henriques, T. B., Junior, P. C. M. L., de Souza, J. C., Pimenta, T. M., Martins, B. D. S., Butzene, S. M. S., Padilha, J. M. S., et al. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1566330 · Cited by 1
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Cortesi, M., Liu, D., Powell, E., Barlow, E. L., Warton, K., Giordano, E., & Ford, C. E. (2025) · Bioengineering & Translational Medicine · doi:10.1002/btm2.70082 · Cited by 1
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Current status of in vitro models for rare gynaecological cancer research
Raos, D., Vučemilo, N., Ozretić, P., & Sabol, M. (2024) · European Journal of Surgical Oncology · doi:10.1016/j.ejso.2024.108549 · Cited by 1
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“In the investigation of the potential interaction between PARK2 and ZNF703 in HGSC cells, immunofluorescent staining and co-IP assays were conducted on OV90 and OVCAR3 cells (two representative HGSOC cell lines [14]) with and without induced overexpression of PARK2 .”
Spasojević, I., Huang, Z., da Silva, W. T. A., Duan, W., Du, L., Chen, C., Cao, J., Zhang, S., Lee, H., Lo, G., et al. (2025) · Oxidative Medicine and Cellular Longevity · doi:10.1155/omcl/6333148 · Cited by 1
“It is thus known as putative low-grade cell line [14, 25].”
The role of bone morphogenetic protein 2 in ovarian cancer migration
Lau, K. S.-K. (2016) · cIRcle (University of British Columbia) · doi:10.14288/1.0307514 · Cited by 1
Gamberi, T. (2019) · Annals of Translational Medicine · doi:10.21037/atm.2019.10.100 · Cited by 1
Anticancer effects of cepharanthine on human ovarian cancer cells
Payon, V. (2016) · Chula Digiverse · doi:10.58837/chula.the.2016.1791 · Cited by 1
Sengupta, D., & Sengupta, K. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.09.02.506330 · Cited by 1
“Numerous studies (85-87) have indicated that the cell line is typical of HGSOC (High-Grade Serous Ovarian Carcinoma).”
BackgroundForgie, B. N., Prakash, R., Marno, D., Abdalbari, F. H., Zorychta, E., Noman, A. S. M., Goyeneche, A. A., Gilbert, L., Burnier, J. V., & Telleria, C. M. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.06.30.735544 · Cited by 1
Analysing Molecular Mechanism Related to Therapy- Resistance in In-vitro Models of Ovarian Cancer
Hahne, J. C., Hönig, A., Engel, J. B., Lampis, A., & Valeri, N. (2016) · InTech eBooks · doi:10.5772/60727
Al-Salmani, K. K. S. (2017) · Leicester Research Archive (University of Leicester)
Cyclin E1 as a therapeutic target in high grade serous ovarian cancer
Au‐Yeung, G. (2017) · Minerva Access (University of Melbourne)
Holzapfel, N. P. (2017) · Queensland University of Technology · doi:10.5204/thesis.eprints.107571
Clark, K. J. (2019) · RIT Scholar Works (Rochester Institute of Technology)
Thibault, B., Thole, A., Basset, C., & Guillermet‐Guibert, J. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/777649
Evaluation of publicly available in vitro drug sensitivity models for ovarian and uterine cancer
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Metadata
- Authors
- Beaufort, C. M., Helmijr, J. C. A., Piskorz, A. M., Hoogstraat, M., Ruigrok-Ritstier, K., Besselink, N., Murtaza, M., van IJcken, W. F. J., Heine, A. A. J., Smid, M., Koudijs, M. J., Brenton, J. D., Berns, E. M. J. J., & Helleman, J.
- Affiliations
- Erasmus MC Cancer Institute (NL)
- University of Cambridge (GB)
- University Medical Center Utrecht (NL)
- Corresponding author
- Berns, Els M. J. J.
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2014-09-17
- Volume
- 9
- Issue
- 9
- Pages
- e103988
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4167545
- OpenAlex
- W2015030879
- Cited by
- 403
- References
- 89
- Citations by year
- 2026: 15 · 2025: 24 · 2024: 30 · 2023: 48 · 2022: 38 · 2021: 54 · 2020: 52 · 2019: 41 · 2018: 27 · 2017: 28 · 2016: 25 · 2015: 21
- FWCI
- 29.95
- Type
- journal article
- Language
- en
- Update notices
- correction (2015-03-23)
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- RePub (Erasmus University Rotterdam) (submittedVersion)
- Funders
- Cancer Research UK (15601)
- Universitair Medisch Centrum Utrecht
- Topics
- Health Sciences › Medicine › Oncology › Ovarian cancer diagnosis and treatment
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Keywords
- epithelial ovarian cancer, ovarian cancer cell lines, morphological subtypes, high-grade serous carcinoma, low-grade serous carcinoma, tumor heterogeneity, metastasis, prognosis, drug response, preclinical models
- MeSH terms
- Carcinoma, Ovarian Epithelial, Female, Humans, Neoplasms, Glandular and Epithelial, Ovarian Neoplasms, Gene Expression Regulation, Neoplastic, MicroRNAs
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