Microfluidic model with air-walls reveals fibroblasts and keratinocytes modulate melanoma cell phenotype, migration, and metabolism
Open accessAbstract
Melanoma evolution is a complex process. The role epidermal keratinocytes and dermal fibroblasts play in this process and the mechanisms involved in tumor-stroma interactions remain poorly understood. Here, we used a microfluidic platform to evaluate the cross-talk between human primary melanoma cells, keratinocytes and dermal fibroblasts. The microfluidic device included multiple circular chambers separated by a series of narrow connection channels. The microdevice design allowed us to develop a new cell patterning method based on air-walls, removing the need for hydrogel barriers, porous membranes, or external equipment. Using this method, we co-cultured melanoma cells in the presence of keratinocytes and/or dermal fibroblasts. The results demonstrated that the presence of dermal fibroblasts and keratinocytes led to changes in melanoma cell morphology and growth pattern. Molecular analysis revealed changes in the chemokine secretion pattern, identifying multiple secreted factors involved in tumor progression. Finally, optical metabolic imaging showed that melanoma cells, fibroblasts, and keratinocytes exhibited different metabolic features. Additionally, the presence of stromal cells led to a metabolic shift in melanoma cells, highlighting the role the skin microenvironment on melanoma evolution.
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- Authors
- Ayuso, J. M., Sadangi, S., Lares, M., Rehman, S., Humayun, M., Denecke, K. M., Skala, M. C., Beebe, D. J., & Setaluri, V.
- Affiliations
- Department of Pathology & Laboratory Medicine
- University of Wisconsin–Madison (US)
- University of Wisconsin System (US)
- Corresponding author
- Setaluri, Vijayasaradhi
- ORCID
- Venue
- Lab on a Chip
- Publisher
- Royal Society of Chemistry (RSC)
- Published
- 2021
- Volume
- 21
- Issue
- 6
- Pages
- 1139-1149
- ISSN
- 1473-0189 (ISSN-L)
- 1473-0197
- PMC
- PMC7990711
- OpenAlex
- W3128844369
- Cited by
- 39
- References
- 41
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 8 · 2023: 9 · 2022: 8 · 2021: 2
- FWCI
- 2.05
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Lab on a Chip (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R01 CA185747, R01 CA164492, R01 CA205101)
- University of Wisconsin-Madison (NIH P30 P30AR066524, AAB7173)
- National Science Foundation (CBET-1642287)
- U.S. Department of Defense (W81XWH-18-PRCRP-IASF (CA181014))
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- melanoma, tumor-stroma interactions, dermal fibroblasts, keratinocytes, cell patterning, co-culture, cell migration, cancer metabolism, chemokine secretion, skin microenvironment, microfluidics
- MeSH terms
- Cells, Cultured, Fibroblasts, Humans, Melanoma, Phenotype, Keratinocytes, Microfluidics, Tumor Microenvironment
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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