It has been proposed that extracellular vesicles (EVs) including exosomes from the diet can be absorbed by the intestinal tract of the consuming organism, be bioavailable in various organs, and exert phenotypic changes. Here, we orally administered bovine milk-derived EVs to mice and demonstrate that milk-derived EVs can survive the harsh degrading conditions of the gut and subsequently be detected in multiple organs. Interestingly, oral administration of milk-derived EVs reduced the primary tumor burden in various cancer models and attenuated cancer cachexia. Intriguingly, in spite of the reduction in primary tumor growth, milk-derived EVs accelerated metastasis in breast and pancreatic cancer mice models. Timing of exosome administration was critical as oral administration after resection of the primary tumor reversed the pro-metastatic effects of milk-derived EVs in breast cancer. Taken together, our study provides novel context-based and opposing role of milk-derived EVs as metastasis inducers and as metastasis blocker.
Samuel et al. Cell, In revision