Melanoma exhibits distinct patterns of organ-specific spread whereby metastasis to the brain generally occurs in young patient populations and metastasis to the liver is more frequent in older populations. However, the cellular cues dictating this phenotype were unknown. Now, Gurung et al. find that age-based variations in stromal lipid species dictate melanoma metastatic tropism to the liver.

Through a series of experiments, the authors revealed that the secretome of young adipocytes upregulates the PI3K pathway in human melanoma cells. Phosphatidylcholines, which were proportionally upregulated in the secretome, were found to induce said pathway activation, promote melanoma cell proliferation and limit both metastatic spread and liver tropism. By contrast, old adipocytes were found to produce more ceramide species, which increased IL-6 secretion, in turn mediating liver tropism.