Impact of the spheroid model complexity on drug response
Open accessAbstract
Pharmaceutical investigators are searching for preclinical models closely resembling the original cancer and predicting clinical outcome. This study compares drug response of three in vitro 3D-drug screening models with different complexity. Tumor cell line spheroids were generated from the cell lines Caco-2, DLD-1, COLO 205, HT-29 and HCT-116, and treated with clinically relevant combination therapies, namely 5-FU/oxaliplatin (FO), 5-FU/irinotecan (FI) and the molecular drugs Cetuximab, Trastuzumab, Vorinostat and Everolimus. Treatment results were compared with spheroids originated from tumor cell lines (Caco-2, DLD-1) co-cultured with stromal cells (PBMCs, cancer-associated fibroblasts of colorectal origin) and spheroids directly prepared from colon cancer tissues. Different microenvironment compositions altered the tumor cell line spheroid response patterns. Adding PBMCs increased resistance to FO treatment by 10-15% in Caco-2 and DLD-1 spheroids but decreased resistance to FI by 16% in DLD-1 spheroids. Fibroblast co-cultures decreased resistance to FI in Caco-2 spheroids by 38% but had no impact on FO. Treatment of colon cancer tissue spheroids revealed three distinct response pattern subgroups not detectable in 3D cell lines models. The cancer tissue spheroid model mimics both tumor characteristics and the stromal microenvironment and therefore is an invaluable screening model for pharmaceutical drug development.
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Spheroids hold great promise for the recapitulation of solid tumors in many relevant aspects.
“Despite their simplicity, they hold great promise for the recapitulation of solid tumors in many relevant aspects [22,29,116,117].”
From The Tumor-on-Chip: Recent Advances in the Development of Microfluidic Systems to Recapitulate the Physiology of Solid Tumors (2019) · cites this paper as [117]
Cites
Accessories to the Crime: Functions of Cells Recruited to the Tumor Microenvironment
Hanahan, D., & Coussens, L. M. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.02.022 · Cited by 4,632 · see citing works
Tournigand, C., André, T., Achille, E., Lledo, G., Flesh, M., Mery-Mignard, D., Quinaux, E., Couteau, C., Buyse, M., Ganem, G., et al. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.05.113 · Cited by 2,915 · see citing works
Luca, A. C., Mersch, S., Deenen, R., Schmidt, S., Messner, I., Schäfer, K.-L., Baldus, S. E., Huckenbeck, W., Piekorz, R. P., Knoefel, W. T., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0059689 · Cited by 341 · see citing works
Kharaishvili, G., Simkova, D., Bouchalova, K., Gachechiladze, M., Narsia, N., & Bouchal, J. (2014) · Cancer Cell International · doi:10.1186/1475-2867-14-41 · Cited by 197 · see citing works
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Three-dimensional culture systems in cancer research: Focus on tumor spheroid model
Nath, S., & Devi, G. R. (2016) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2016.03.013 · Cited by 919 · see citing works
Nunes, A. S., Barros, A. S., Costa, E. C., Moreira, A. F., & Correia, I. J. (2019) · Biotechnology and Bioengineering · doi:10.1002/bit.26845 · Cited by 721 · see citing works
Three-Dimensional Spheroids as In Vitro Preclinical Models for Cancer Research
Pinto, B., Henriques, A. C., Silva, P. M. A., & Bousbaa, H. (2020) · Pharmaceutics · doi:10.3390/pharmaceutics12121186 · Cited by 440 · see citing works
Däster, S., Amatruda, N., Calabrese, D., Ivanek, R., Turrini, E., Droeser, R. A., Zajac, P., Fimognari, C., Spagnoli, G. C., Iezzi, G., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.13857 · Cited by 281 · see citing works
Barbosa, M. A. G., Xavier, C. P. R., Pereira, R. F., Petrikaitė, V., & Vasconcelos, M. H. (2021) · Cancers · doi:10.3390/cancers14010190 · Cited by 285 · see citing works
Melissaridou, S., Wiechec, E., Magan, M., Jain, M. V., Chung, M. K., Farnebo, L., & Roberg, K. (2019) · Cancer Cell International · doi:10.1186/s12935-019-0733-1 · Cited by 262 · see citing works
Trujillo-de Santiago, G., Flores-Garza, B. G., Tavares-Negrete, J. A., Lara-Mayorga, I. M., González-Gamboa, I., Zhang, Y. S., Rojas-Martínez, A., Ortiz-López, R., & Álvarez, M. M. (2019) · Materials · doi:10.3390/ma12182945 · Cited by 184 · see citing works
“Despite their simplicity, they hold great promise for the recapitulation of solid tumors in many relevant aspects [22,29,116,117].”
BackgroundHuang, B.-W., & Gao, J.-Q. (2018) · Journal of Controlled Release · doi:10.1016/j.jconrel.2017.12.005 · Cited by 174 · see citing works
Tumor cells and their crosstalk with endothelial cells in 3D spheroids
Shoval, H., Karsch-Bluman, A., Brill-Karniely, Y., Stern, T., Zamir, G., Hubert, A., & Benny, O. (2017) · Scientific Reports · doi:10.1038/s41598-017-10699-y · Cited by 138 · see citing works
Engineering approaches for studying immune-tumor cell interactions and immunotherapy
Shelton, S. E., Nguyen, H. T., Barbie, D. A., & Kamm, R. D. (2021) · iScience · doi:10.1016/j.isci.2020.101985 · Cited by 93 · see citing works
Fibroblast-associated tumour microenvironment induces vascular structure-networked tumouroid
Lee, S. W., Kwak, H. S., Kang, M.-H., Park, Y.-Y., & Jeong, G. S. (2018) · Scientific Reports · doi:10.1038/s41598-018-20886-0 · Cited by 68 · see citing works
- Authors
- Hoffmann, O. I., Ilmberger, C., Magosch, S., Joka, M., Jauch, K.-W., & Mayer, B.
- Affiliations
- Ludwig-Maximilians-Universität München (DE)
- Corresponding author
- Mayer, Barbara
- Venue
- Journal of Biotechnology
- Publisher
- Elsevier BV
- Published
- 2015-07
- Volume
- 205
- Pages
- 14-23
- ISSN
- 0168-1656 (ISSN-L)
- OpenAlex
- W2057853951
- Cited by
- 125
- References
- 4
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 7 · 2023: 8 · 2022: 17 · 2021: 12 · 2020: 21 · 2019: 17 · 2018: 12 · 2017: 8 · 2016: 10 · 2015: 4
- FWCI
- 4.95
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biotechnology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Bundesministerium für Bildung und Forschung
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Physical Sciences › Mathematics › Modeling and Simulation › Mathematical Biology Tumor Growth
- Keywords
- tumor spheroids, 3D cell culture models, colorectal cancer, drug response, combination chemotherapy, 5-fluorouracil, oxaliplatin, irinotecan, cetuximab, trastuzumab, vorinostat, everolimus, cancer-associated fibroblasts, peripheral blood mononuclear cells, tumor microenvironment, drug resistance, Caco-2 cells, DLD-1 cells, HCT116 cells, HT-29 cells, COLO 205
- MeSH terms
- Everolimus, Cetuximab, Trastuzumab, Irinotecan, Oxaliplatin, Vorinostat, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Camptothecin, Cell Survival, Cells, Cultured, Fluorouracil, Humans, Hydroxamic Acids, Organoplatinum Compounds, Tumor Cells, Cultured, Treatment Outcome, Stromal Cells, Spheroids, Cellular, Coculture Techniques, Caco-2 Cells, HT29 Cells, HCT116 Cells, Cell Line, Tumor, Tumor Microenvironment
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