Melanoma incidence and mortality is higher in aged men than women, and the mechanisms underlying this are largely unexplored. Chhabra et al. now report age- and sex-dependent changes in skin fibroblasts that drive melanoma aggressiveness.

To assess if fibroblast changes affect tumours, melanoma cells were exposed to conditioned media from the four fibroblast groups. Media from aged male fibroblasts most strongly increased invasion and induced a phenotypic switch to a highly invasive, slow-cycling state with high AXL expression. These effects were mediated by a WNT5A-dependent increase in oxidative stress in melanoma cells.