Extracellular vesicles from a model of melanoma cancer-associated fibroblasts induce changes in brain microvascular cells consistent with pre-metastatic niche priming.

A key characteristic of these tumours is crosstalk between melanoma cells and cells of the tumour microenvironment (TME), such as cancer associated fibroblasts (CAFs). The role of melanoma-derived small extracellular vesicles (sEVs) in potentiating CAFs has been studied extensively, however the role of CAF sEVs in regulation of the local TME and distal pre-metastatic niche (PMN) is less clear.

Here, we demonstrate that sEVs derived from an in vitro model of melanoma CAFs alter melanoma to promote oncogenic parameters within models of the TME and target a model of the brain PMN to promote changes associated with melanoma extravasation. Cargo profiling of these sEVs found significant differential expression of proteins, and RNA associated with pre-metastatic niche remodelling and unfavourable outcomes in patients.