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Updated: Nov 19, 2025
A 3D Organotypic Melanoma Spheroid Skin Model
Published on: May 18, 2018
Three-dimensional multicellular cell culture for anti-melanoma drug screening: focus on tumor microenvironment
Najla Adel Saleh1, Michele Patrícia Rode1, Jelver Alexander Sierra2
1Departamento de Ciências Farmacêuticas, GEIMM-Grupo de Estudos de Interações entre Micro e Macromoléculas, Universidade Federal de Santa Catarina, S/N Centro de Ciências da Saúde Bloco H - 3° andar, sala H302-Bairro Trindade, Florianópolis, Santa Catarina CEP: 88040-900 Brazil.
Abstract:
The development of new treatments for malignant melanoma, which has the worst prognosis among skin neoplasms, remains a challenge. The tumor microenvironment aids tumor cells to grow and resist to chemotherapeutic treatment. One way to mimic and study the tumor microenvironment is by using three-dimensional (3D) co-culture models (spheroids). In this study, a melanoma heterospheroid model composed of cancer cells, fibroblasts, and macrophages was produced by liquid-overlay technique using the agarose gel. The size, growth, viability, morphology, cancer stem-like cells population and inflammatory profile of tumor heterospheroids and monospheroids were analyzed to evaluate the influence of stromal cells on these parameters. Furthermore, dacarbazine cytotoxicity was evaluated using spheroids and two-dimensional (2D) melanoma model. After finishing the experiments, it was observed the M2 macrophages induced an anti-inflammatory microenvironment in heterospheroids; fibroblasts cells support the formation of the extracellular matrix, and a higher percentage of melanoma CD271 was observed in this model. Additionally, melanoma spheroids responded differently to the dacarbazine than the 2D melanoma culture as a result of their cellular heterogeneity and 3D structure. The 3D model was shown to be a fast and reliable tool for drug screening, which can mimic the in vivo tumor microenvironment regarding interactions and complexity.
Insights
This study developed a 3D melanoma model with cancer cells, fibroblasts, and macrophages. This advanced model accurately mimics the tumor microenvironment, improving drug screening for malignant melanoma treatments.
Area of Science:
- Oncology
- Biomedical Engineering
- Cell Biology
Background:
- Malignant melanoma poses a significant treatment challenge due to its poor prognosis.
- The tumor microenvironment (TME) plays a crucial role in melanoma growth and therapeutic resistance.
- Three-dimensional (3D) co-culture models, such as spheroids, offer a way to study the TME.
Purpose of the Study:
- To develop and characterize a melanoma heterospheroid model incorporating cancer cells, fibroblasts, and macrophages.
- To investigate the influence of stromal cells on spheroid characteristics and inflammatory profiles.
- To evaluate the efficacy of dacarbazine in the 3D model compared to traditional 2D cultures.
Main Methods:
- A melanoma heterospheroid model was created using a liquid-overlay technique with agarose gel.
- Analysis included spheroid size, growth, viability, morphology, cancer stem-like cell population, and inflammatory markers.
- Dacarbazine cytotoxicity was assessed in both 3D spheroids and 2D melanoma cultures.
Main Results:
- Heterospheroids exhibited an anti-inflammatory microenvironment induced by M2 macrophages.
- Fibroblasts promoted extracellular matrix formation, and increased melanoma CD271 expression was noted.
- Melanoma spheroids demonstrated differential responses to dacarbazine compared to 2D cultures due to structural and cellular complexity.
Conclusions:
- The 3D heterospheroid model effectively mimics the in vivo tumor microenvironment's complexity and cell interactions.
- This 3D model serves as a rapid and reliable platform for preclinical drug screening in melanoma.
- Understanding TME components is vital for developing effective melanoma therapies.
