ArticleInternational journal of molecular sciences2022
Human Papillary and Reticular Fibroblasts Show Distinct Functions on Tumor Behavior in 3D-Organotypic Cultures Mimicking Melanoma and HNSCC.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 10 citations in OpenAlex.
- Fibroblast-derived matrix human skin equivalents reveal distinct roles for papillary and reticular fibroblasts in human skin barrier integrity and aging.Scientific reports · 2026Article
- Role of Fibroblast-Immune Crosstalk in Kidney, Lung, and Skin Tertiary Lymphoid Structures.Immunological reviews · 2025Review
- Electrospinning strategies targeting fibroblast for wound healing of diabetic foot ulcers.APL bioengineering · 2025Review
- Spatiotemporal characterization of extracellular matrix maturation in human artificial stromal-epithelial tissue substitutes.BMC biology · 2024Article
- The development of in vitro organotypic 3D vulvar models to study tumor-stroma interaction and drug efficacy.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Fibroblasts in Diabetic Foot Ulcers.International journal of molecular sciences · 2024Review
- Trichothiodystrophy-associated MPLKIP maintains DBR1 levels for proper lariat debranching and ectodermal differentiation.EMBO molecular medicine · 2023Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human dermis can be morphologically divided into the upper papillary and lower reticular dermis. Previously, we demonstrated that papillary (PFs) and reticular (RFs) fibroblasts show distinct morphology and gene expression profiles. Moreover, they differently affect tumor invasion and epithelial-to-mesenchymal transition (EMT) in in vitro 3D-organotypic cultures of cutaneous squamous cell carcinoma (cSCC). In this study, we examined if these distinct effects of PFs and RFs can be extrapolated in other epithelial/non-epithelial tumors such as melanoma and head and neck squamous cell carcinoma (HNSCC). To this end, 3D-Full-Thickness Models (FTMs) were established from melanoma (AN and M14) or HNSCC cell lines (UM-SCC19 and UM-SCC47) together with either PFs or RFs in the dermis. The interplay between tumor cells and different fibroblasts was investigated. We observed that all the tested tumor cell lines showed significantly stronger invasion in RF-FTMs compared to PF-FTMs. In addition, RF-FTMs demonstrated more tumor cell proliferation, EMT induction and basement membrane disruption. Interestingly, RFs started to express the cancer-associated fibroblast (CAF) biomarker α-SMA, indicating reciprocal interactions eventuating in the transition of RFs to CAFs. Collectively, in the melanoma and HNSCC FTMs, interaction of RFs with tumor cells promoted EMT and invasion, which was accompanied by differentiation of RFs to CAFs.
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