A preclinical model of cutaneous melanoma based on reconstructed human epidermis

Abstract

Malignant melanoma is among the tumor entities with the highest increase of incidence worldwide. To elucidate melanoma progression and develop new effective therapies, rodent models are commonly used. While these do not adequately reflect human physiology, two-dimensional cell cultures lack crucial elements of the tumor microenvironment. To address this shortcoming, we have developed a melanoma skin equivalent based on an open-source epidermal model. Melanoma cell lines with different driver mutations were incorporated into these models forming distinguishable tumor aggregates within a stratified epidermis. Although barrier properties of the skin equivalents were not affected by incorporation of melanoma cells, their presence resulted in a higher metabolic activity indicated by an increased glucose consumption. Furthermore, we re-isolated single cells from the models to characterize the proliferation state within the respective model. The applicability of our model for tumor therapeutics was demonstrated by treatment with a commonly used v-raf murine sarcoma viral oncogene homolog B (BRAF) inhibitor vemurafenib. This selective BRAF inhibitor successfully reduced tumor growth in the models harboring BRAF-mutated melanoma cells. Hence, our model is a promising tool to investigate melanoma development and as a preclinical model for drug discovery.

The influence of viscosity of hydrogels on the spreading and migration of cells in 3D bioprinted skin cancer models

“…The molecular differences between the cell types can enable the development of targeted therapies ( Caputo et al, 2011 ). However, melanoma cells cultured in 2D represent a reductionist approach, since cells proliferate much faster than in vivo , do not represent the in vivo microenvironment, and are more sensitive to drugs ( Leikeim et al, 2022 ).…”