The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
Development of a human three-dimensional organotypic skin-melanoma spheroid model for in vitro drug testing
Open accessAbstract
Despite remarkable efforts, metastatic melanoma (MM) still presents with significant mortality. Recently, mono-chemotherapies are increasingly replenished by more cancer-specific combination therapies involving death ligands and drugs interfering with cell signaling. Still, MM remains a fatal disease because tumors rapidly develop resistance to novel therapies thereby regaining tumorigenic capacity. Although genetically engineered mouse models for MM have been developed, at present no model is available that reliably mimics the human disease and is suitable for studying mechanisms of therapeutic obstacles including cell death resistance. To improve the increasing requests on new therapeutic alternatives, reliable human screening models are demanded that translate the findings from basic cellular research into clinical applications. By developing an organotypic full skin equivalent, harboring melanoma tumor spheroids of defined sizes we have invented a cell-based model that recapitulates both the 3D organization and multicellular complexity of an organ/tumor in vivo but at the same time accommodates systematic experimental intervention. By extending our previous findings on melanoma cell sensitization toward TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) by co-application of sublethal doses of ultraviolet-B radiation (UVB) or cisplatin, we show significant differences in the therapeutical outcome to exist between regular two-dimensional (2D) and complex in vivo-like 3D models. Of note, while both treatment combinations killed the same cancer cell lines in 2D culture, skin equivalent-embedded melanoma spheroids are potently killed by TRAIL+cisplatin treatment but remain almost unaffected by the TRAIL+UVB combination. Consequently, we have established an organotypic human skin-melanoma model that will facilitate efforts to improve therapeutic outcomes for malignant melanoma by providing a platform for the investigation of cytotoxic treatments and tailored therapies in a more physiological setting.
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“In melanoma spheroids, for example, fibroblasts have been shown to accumulate in low-oxygen regions and upregulate genes associated with ECM production and wound response [288].”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [288]
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Citations
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Metadata
- Authors
- Vörsmann, H., Groeber, F., Walles, H., Busch, S., Beissert, S., Walczak, H., & Kulms, D.
- Affiliations
- University of Stuttgart (DE)
- Fraunhofer Institute for Interfacial Engineering and Biotechnology (DE)
- Technische Universität Dresden (DE)
- University College London (GB)
- Corresponding author
- Kulms, D
- Venue
- Cell Death & Disease
- Published
- 2013-07-11
- Volume
- 4
- Issue
- 7
- Pages
- e719-e719
- ISSN
- 2041-4889 (ISSN-L)
- PMC
- PMC3730422
- OpenAlex
- W2042222655
- Cited by
- 168
- References
- 44
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 14 · 2023: 8 · 2022: 18 · 2021: 12 · 2020: 15 · 2019: 14 · 2018: 16 · 2017: 14 · 2016: 16 · 2015: 13 · 2014: 11 · 2013: 1
- FWCI
- 6.12
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- www.springer.com/tdm (unspecified)
- Locations
- Cell Death and Disease (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Fraunhofer-Publica (Fraunhofer-Gesellschaft) (submittedVersion)
- Funders
- Deutsche Krebshilfe
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Oncology › Cutaneous Melanoma Detection and Management
- Keywords
- metastatic melanoma, 3D tumor models, TRAIL sensitization, cisplatin, UV-B radiation, combination therapy, drug resistance, in vitro drug testing, tumor necrosis factor-related apoptosis-inducing ligand
- MeSH terms
- Antineoplastic Agents, Cisplatin, Drug Screening Assays, Antitumor, Drug Synergism, Humans, Melanoma, Skin Neoplasms, Skin, Artificial, Spheroids, Cellular, Coculture Techniques, Cell Line, Tumor, TNF-Related Apoptosis-Inducing Ligand
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