# Development of a 3D Skin Model for Studying Melanoma Progression

**Authors:** Dragana P. C. de Barros, Sara Ventura, Madalena Duque, Vanessa Ribeiro, Ana Sofia Lopes, Rita Zilhão, Ana Rita Carlos, Abel Oliva

PMC · DOI: 10.3390/cells15040379 · 2026-02-23

## TL;DR

A 3D skin model was developed to study melanoma progression and drug responses, offering a more realistic alternative to animal testing.

## Contribution

The development of a 3D melanoma skin model that mimics tumor progression and immune evasion traits.

## Key findings

- The 3D model supports melanoma cell invasion and recapitulates key features like ECM remodeling and EMT.
- The model exhibits cytokine profiles similar to those seen in melanoma inflammation and immune evasion.
- The model can be used for personalized medicine strategies using patient-derived cells.

## Abstract

Despite advances in the treatment of cutaneous melanoma, there is still a high percentage of patients who fail to respond or develop resistance to treatment. Establishing robust in vitro melanoma models will enable mechanism-based drug screening while reducing animal testing. In this work, a three-dimensional (3D) melanoma skin model (3DMSM) was developed on a porous scaffold. The culture of three melanoma cell lines (SKMEL-1, A375, and G361) in co-culture with human fibroblasts, melanocytes, and keratinocytes allowed the formation of the dermis, and stratified epidermis. Tumors were established in this model using two methodologies: adding previously formed melanoma cell aggregates (CA) or seeding melanoma cells directly into the dermis (CD). In this model, melanoma cells remain in their original microenvironment and, after proliferation, invade the basal layer. The model recapitulates correct melanocyte localization, epidermal disruption, extracellular matrix (ECM) remodeling, including collagen deposition, and epithelial-to-mesenchymal transition (EMT). Additionally, the cytokine profiles studied indicate that the model could mirror the inflammatory and immune-evasive traits of melanoma. Overall, 3DMSM provides a useful tool for understanding the mechanisms of melanoma progression and invasion, and for developing personalized medicine strategies through the implementation of a patient-derived model.

## Linked entities

- **Proteins:** COL3A1 (collagen type III alpha 1 chain)
- **Diseases:** melanoma (MONDO:0005105)
- **Species:** Homo sapiens (taxon 9606)

## Full-text entities

- **Genes:** CDH1 (cadherin 1) [NCBI Gene 999] {aka Arc-1, BCDS1, CD324, CDHE, ECAD, LCAM}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, FN1 (fibronectin 1) [NCBI Gene 2335] {aka CIG, ED-B, FINC, FN, FNZ, GFND}, BRAF (B-Raf proto-oncogene, serine/threonine kinase) [NCBI Gene 673] {aka B-RAF1, B-raf, BRAF-1, BRAF1, NS7, RAFB1}, TYR (tyrosinase) [NCBI Gene 7299] {aka ATN, CMM8, OCA1, OCA1A, OCAIA, SHEP3}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, VIM (vimentin) [NCBI Gene 7431], IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, IVL (involucrin) [NCBI Gene 3713], CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, KRT14 (keratin 14) [NCBI Gene 3861] {aka CK14, EBS1, EBS1A, EBS1B, EBS1C, EBS1D}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, S100B (S100 calcium binding protein B) [NCBI Gene 6285] {aka NEF, S100, S100-B, S100beta}, SOX10 (SRY-box transcription factor 10) [NCBI Gene 6663] {aka DOM, PCWH, SOX-10, WS2E, WS4, WS4C}, KRT10 (keratin 10) [NCBI Gene 3858] {aka BCIE, BIE, CK10, EHK, EHK2, EHK2A}
- **Diseases:** invasive (MESH:D009361), cutaneous melanoma (MESH:C562393), aggressiveness (MESH:D010554), ALI (MESH:D004618), benign nevi (MESH:D009506), metastasis (MESH:D009362), skin cancer (MESH:D012878), HEM (MESH:D006470), Cancer (MESH:D009369), fibrosis (MESH:D005355), 3DMSM-CA (MESH:D008545), inflammation (MESH:D007249), injury to (MESH:D014947)
- **Chemicals:** pen (MESH:C058388), 4,6-diamidino-2-Phenylindole (MESH:C007293), Formalin (MESH:D005557), glucose (MESH:D005947), H (MESH:D006859), DAB (MESH:C000469), Eosin (MESH:D004801), melanin (MESH:D008543), polystyrene (MESH:D011137), CO2 (MESH:D002245), citrate (MESH:D019343), Hematoxylin (MESH:D006416), penicillin (MESH:D010406), H&amp;E (MESH:D006371), EDTA (-), ethanol (MESH:D000431), CaCl2 (MESH:D002122), CCK-8 (MESH:D012844), streptomycin (MESH:D013307), xylene (MESH:D014992), Trypan blue (MESH:D014343), paraffin (MESH:D010232)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** V600E
- **Cell lines:** SKMEL-1:5 — Homo sapiens (Human), Cutaneous melanoma, Cancer cell line (CVCL_0527), A375 — Homo sapiens (Human), Amelanotic melanoma, Cancer cell line (CVCL_0132), HKGS — Homo sapiens (Human), Transformed cell line (CVCL_T291), HEM-DP — Homo sapiens (Human), Moyamoya disease, Induced pluripotent stem cell (CVCL_A4GC), 3DMSM — Mus musculus (Mouse), Mouse melanoma, Cancer cell line (CVCL_B0CF), -CD — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_5731), HEK — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_9T09), A2058 — Homo sapiens (Human), Amelanotic melanoma, Cancer cell line (CVCL_1059), CCK8 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_2873), A375:5 — Homo sapiens (Human), Amelanotic melanoma, Cancer cell line (CVCL_2294), SK MEL 1 — Homo sapiens (Human), Melanoma, Cancer cell line (CVCL_0068), ATCC  TCP-1013 — Homo sapiens (Human), Finite cell line (CVCL_LK64), TCP-1013 — Homo sapiens (Human), Induced pluripotent stem cell (CVCL_B3UR), G361 — Homo sapiens (Human), Melanoma, Cancer cell line (CVCL_1220)

## Figures

15 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12939632/full.md

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Source: https://tomesphere.com/paper/PMC12939632