# Applications of Tumor Cells in an _In Vitro_ 3D Environment
## 7 Applications of 3D Models of Cancer Cells
### Melanocytes  
The vital role of melanocytes in the skin comes not only from their ability to synthesize melanin, which allows skin pigmentation. More importantly, pigment absorbs the harmful UV radiation that penetrates the skin and protects the cells from DNA damage. The elongated dendritic extensions of melanocytes that allow melanin transfer from the _stratum basale_ to more distant epidermal layers [92] also allow for the transfer of growth factors from keratinocytes, stimulating melanocyte proliferation and differentiation [106]. Moreover, when melanocytes are co-cultured with keratinocytes and fibroblasts, the latter cells secrete various factors that support melanocyte migration and survival and allow melanocytes to return to their typical phenotypic characteristics, such as high proliferation rates and active expression of various melanoma-associated antigens [107]. Interestingly, in some hSEs, melanocytes have also been reported to mimic naive melanocytes by protecting the basal keratinocytes against UVB-induced apoptosis [108].  
For a long time, 2D monolayer cultures were regarded as the standard models for studying melanocyte or melanoma biology but are now considered quite inferior. This is caused by culture-induced changes in cell morphology and gene expression patterns that alter the phenotype and behavior of the cells _in situ_. Indeed, the intricate network of cell-cell interactions in native skin requires more advanced systems mimicking cellular communication in a more realistic way. The development of 3D hSEs allows for complex interactions between different cells and between cells and matrix to occur, minimizing the emergence of culture artifacts [109].  
One of the most common ways to construct 3D hSEs involves using a collagen-based dermal matrix. A better alternative could be a broadly emerging technology known as 3D bioprinting, which allows for the production of full-thickness hSEs by sequentially printing single melanocytes and keratinocytes on top of dermal equivalents. This not only resolves the problem of drug absorption in the collagen but also allows a more precise allocation of the cells in the epidermis.  
The neural crest stem cell (NCSC) origin of melanocytes underlies the ability of metastasizing melanoma cells to both migrate to and thrive in the brain and other major organs, including the lungs [97]. Common mutations in genes involved in melanomas include BRAF, NRAS, and NF-1. Significant treatment efficacy has been observed with some regimens, including targeted- and immune-based therapeutic strategies. The understanding of the genetic and non-genetic mechanisms in melanomas has increased, which has set the scene for further technological developments to achieve more advanced _in vitro_ cell culture models. Another significant aspect of melanocytes grown in 3D skin reconstruction is that they exhibit homeostasis and progression similar to what is observed in the skin of patients [97]. Moreover, when incorporating melanoma cells into 3D skin reconstructions, they exhibit aggressiveness analogous to their action in patients [97]. Recently, [PERSON] et al. demonstrated that melanoma cells use melanosomes to communicate with fibroblasts at the early stages of development, resulting in CAF formation [110].