Tumor-secreted factors induce aberrant accumulation of vitamin A-enriched lipid droplets in the liver.

Cancer is increasingly recognized as a systemic disease, extending beyond local alterations to systemic alterations in distant organs through the release of various factors that promote tumor progression and metastasis. Here, we applied hyperspectral stimulated Raman scattering (hSRS) microscopy to study metabolic alterations in the liver driven by distant tumors, revealing unprecedented accumulation of vitamin A-enriched lipid droplets. Quantitative spectral analysis uncovered increased unsaturation levels and abnormal vitamin A ester. Notably, inhibition of secretory pathways in remote tumors effectively abrogated these metabolic alterations, with FABP5 in tumor-derived extracellular vesicles identified as a key mediator. These findings uncover a unique aspect of cancer progression mechanisms, implicating tumor-driven systemic lipid metabolic remodeling and vitamin A dysregulation in metastatic progression and therapeutic response.