Nutrients such as fatty acids are known to sustain cancer progression and metastasis, however, whether aberrant disease processes or the diet affects nutrient availability in organs and contributes to the formation of a metastasis-permissive, pre-metastatic niche was unknown. Now, Altea-Manzanoetal. reveal that factors secreted by primarybreast tumours or high-fat diet (HFD) feeding enriches the fatty acid palmitate in distant organs and show that in palmitate-rich environments, breast cancer cells have increased p65 acetylation, metastasis-promoting NF-kB signalling and metastasis formation. First, the authors found that the interstitial fluid of both mouse liver and lung as well as of human non-malignant lung tissue is rich in palmitate-and oleate-containinglipids. The levels of palmitate and oleate were further increased by HFD feeding, causing increased metastatic colonization and growth of breast cancer cells in liver and lung tissue. In experimental and spontaneous mouse models of pre-metastatic niche formation, palmitate, but not oleate, was increased in the lung interstitial fluid. No changes in fatty acid concentration were detected in the liver. A similar increase in palmitate during pre-metastatic niche formation was observed in interstitial fluid samples of patients with breast cancer compared with samples of patients who are cancer-free.
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