The skin microbiome, which comprises bacteria, fungi, mites, and viruses, has been demonstrated to play a critical role in skin homeostasis and disorders. The contribution of the skin microbiome to various skin cancer types, including melanoma, gained increasing attention, as current studies revealed an altered composition of bacterial communities at melanoma sites compared to healthy skin. However, the underlying mechanisms of the complex interplay between the skin microbiome and melanoma progression remain elusive.
We established a co-culture system capable to study host microbiome interactions during melanoma progression in situ. The system is based on the commercially available Melanoma model from MatTek colonized with skin bacteria obtained from skin swabs from a healthy volunteer.
The melanoma models showed a stable co-colonization over the cultivation period of 12 days, with no transcriptional activation of bacterial defense pathways. 16S rRNA gene amplicon sequencing indicated reduced bacterial diversity with Streptococcus being the most abundant genera on the last day of cultivation. Pathways related to melanoma progression, such as RAF/MAP and PI3K kinase, were induced in the transcriptome of colonized models. Those findings correlate with the increased release of cytokines GM-CSF, VEGF, and PIGF, which promote angiogenesis, and melanoma markers MIA and S100B. Additionally, epithelial-mesenchymal transition was active in colonized skin models.
As a proof of concept, the results indicate a clear impact of microbial skin colonization on melanoma tumorigenesis, thereby providing an elegant method to elucidate the microbiome"s impact on cancer development. As a first approach, we colonized 3D melanoma models with a defined bacterial community that included both typical commensal bacteria and pathogens such as Staphylococcus aureus and Corynebacterium striatum, which were found to be abundant on melanoma sites. The initial results indicated more stable models regarding bacterial cell count in the presence of the bacterial mixture containing the pathogens compared to the mixture without, which might affect the progression of melanoma.