Bacterial colonization of 3D melanoma skin models

Melanoma represents the most lethal form of skin cancer, with rising numbers of recorded annual incidences worldwide. In an effort to better understand the factors driving melanoma development, several new risk factors have come into focus, including the skin microbiome. Although previous studies demonstrated melanoma sites to feature an altered microbiome composition, the underlying mechanisms remain elusive. Technically, this is challenging to address. Therefore, we established a novel co-culture system capable of studying human host-microbe interactions during melanoma progression in situ. The system comprises a commercial 3D melanoma skin model, which is cultivated in an air-liquid interface configuration. On this setup we applied apical a diverse bacterial community from healthy human skin. We aimed to examine if and how bacterial colonization changes during co-cultivation and if melanoma progression is affected. The inoculated models showed a successful co-colonization over a period of 12 days, with a decreasing bacterial diversity over the cultivation time. Transcriptome profiles of the skin models revealed marked differences compared to uncolonized controls. Notably, several pathways involved in melanoma progression, such as MAPK and PI3K, were upregulated. The respective models also showed clear signs of active epithelial-mesenchymal transition together with an increased release of the cytokines VEGF, PIGF, and GM-CSF, and the typical melanoma markers MIA and S100B. As a proof of concept, the results indicate a clear effect of microbial skin colonization on melanoma progression. The data also crucially demonstrate the potential of the corresponding co-culture model for further host-microbe interactions in the context of melanoma promotion and progression.