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A 3D Organotypic Melanoma Spheroid Skin Model
Published on: May 18, 2018
A bioengineered tumor matrix-based scaffold for the evaluation of melatonin efficacy on head and neck squamous cancer
Julia López de Andrés1,2,3,4, César Rodríguez-Santana2,5,6,7, Laura de Lara-Peña1,2,3,4
1Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research (CIBM), University of Granada, Granada, Spain.
Abstract:
Head and neck squamous cell carcinoma (HNSCC) presents a significant challenge worldwide due to its aggressiveness and high recurrence rates post-treatment, often linked to cancer stem cells (CSCs). Melatonin shows promise as a potent tumor suppressor; however, the effects of melatonin on CSCs remain unclear, and the development of models that closely resemble tumor heterogeneity could help to better understand the effects of this molecule. This study developed a tumor scaffold based on patient fibroblast-derived decellularized extracellular matrix that mimics the HNSCC microenvironment. Our study investigates the antitumoral effects of melatonin within this context. We validated its strong antiproliferative effect on HNSCC CSCs and the reduction of tumor invasion and migration markers, even in a strongly chemoprotective environment, as it is required to increase the minimum doses necessary to impact tumor viability compared to the non-scaffolded tumorspheres culture. Moreover, melatonin exhibited no cytotoxic effects on healthy cells co-cultured in the tumor hydrogel. This scaffold-based platform allows an in vitro study closer to HNSCC tumor reality, including CSCs, stromal component, and a biomimetic matrix, providing a new valuable research tool in precision oncology.
Insights
Melatonin effectively suppresses head and neck squamous cell carcinoma (HNSCC) cancer stem cells (CSCs) in a novel biomimetic scaffold. This research tool enhances understanding of melatonin
Area of Science:
- Oncology
- Biomaterials Science
- Cancer Research
Background:
- Head and neck squamous cell carcinoma (HNSCC) is aggressive with high recurrence rates, often driven by cancer stem cells (CSCs).
- Melatonin, a potential tumor suppressor, has unclear effects on HNSCC CSCs.
- Accurate models are needed to study melatonin's impact on tumor heterogeneity.
Purpose of the Study:
- To investigate the antitumoral effects of melatonin on HNSCC CSCs within a biomimetic microenvironment.
- To develop and validate a novel scaffold mimicking the HNSCC tumor microenvironment for in vitro studies.
- To assess melatonin's efficacy and safety in a more realistic tumor model.
Main Methods:
- Developed a tumor scaffold using patient fibroblast-derived decellularized extracellular matrix to mimic the HNSCC microenvironment.
- Cultured HNSCC CSCs and healthy cells within the scaffold.
- Investigated the antiproliferative and anti-invasion effects of melatonin on HNSCC CSCs.
- Assessed the cytotoxic effects of melatonin on co-cultured healthy cells.
Main Results:
- Melatonin demonstrated a strong antiproliferative effect on HNSCC CSCs within the scaffold.
- Melatonin reduced tumor invasion and migration markers, even in a chemoprotective environment.
- Higher melatonin doses were required in the scaffold compared to non-scaffolded cultures.
- Melatonin showed no cytotoxic effects on healthy cells co-cultured in the tumor hydrogel.
Conclusions:
- The developed scaffold provides a realistic in vitro model for studying HNSCC, including CSCs and stromal components.
- Melatonin exhibits significant antitumoral effects against HNSCC CSCs in a biomimetic environment.
- This platform is a valuable tool for precision oncology research and drug development for HNSCC.
