A study has confirmed the importance of anti-inflammatory cytokine IL-6

Malign melanoma is one of the most dangerous forms of skin cancer. Its origins are often linked to DNA damage due to the ultraviolet part of sunlight. Of key importance for appearance of the melanoma are skin ageing and age, two factors which have an effect on the skin tissue microenvironment. Research shows that the ageing of skin fibroblasts can speed up tumour progression.

Scientists gathered in the Centre for Tumour Ecology of the First Faculty of Medicine of the Charles University, headed by Professor MUDr. Karel Smetana, DrSc., have, within the framework of collaboration with the Institute of Molecular Genetics of the Czech Academy of Sciences and the University of Chemistry and Technology in Prague, engaged in research of the functioning of fibroblasts in the microenvironment of heterogenous spheroids of the melanoma. The resulting study was published in November 2020 in the Cancers journal with impact factor 6.126 (Q1).

Authors of the study created 3D models of heterogenous spheroids of the melanoma using healthy normal fibroblasts from the skin of a young donor and compared them with fibroblasts from the skin of an adult who had been exposed to the sun. Subsequently, they analysed the spheroids using a wide range of methods including single-cell sequencing with advanced bioinformatic analysis. Using this method, they were able to identify molecules that could be relevant to contact between the fibroblasts and cancer cells. The analysis has mapped and differentiated in the melanoma spheroids three functional clusters of fibroblasts. They differ in the a) expression of genes linked to the production of extracellular matrix, b) their role in interaction with tumour-associated anti-inflammatory factors, and c) in signalling using the TGF-β protein superfamily. Scientists detected an increased deregulation of gene transcription in cells damaged by sunlight, thereby confirming that the anti-inflammatory cytokine IL-6 importantly boosts the invasion of melanoma into the extracellular matrix. This also confirms that aspects of ageing are of crucial importance for reliable 3D modelling of melanoma in vitro. ‘This study is the result of intensive and broad collaboration of anatomists, dermatologists, pathologists, molecular geneticists, and bioinfomatics experts,’ says Professor Smetana, head of the Institute of Anatomy of the First Faculty of Medicine of the CU, about this important result of team research.