Oral administration of bovine milk-derived extracellular vesicles induces senescence in the primary tumor but accelerates cancer metastasis

Samuel, Monisha, Fonseka, Pamali, Sanwlani, Rahul, Gangoda, Lahiru, Chee, Sing Ho, Keerthikumar, Shivakumar, Spurling, Alex, Chitti, Sai V, Zanker, Damien ORCID: 0000-0003-1163-9902, Ang, Ching-Seng, Atukorala, Ishara, Kang, Taeyoung, Shahi, Sanjay, Marzan, Akbar L, Nedeva, Christina, Vennin, Claire, Lucas, Morghan C, Cheng, Lesley, Herrmann, David ORCID: 0000-0002-9514-7501, Pathan, Mohashin, Chisanga, David ORCID: 0000-0002-0421-3957, Warren, Sean C ORCID: 0000-0002-5253-7147, Zhao, Kening, Abraham, Nidhi, Anand, Sushma, Boukouris, Stephanie, Adda, Christopher G, Jiang, Lanzhou, Shekhar, Tanmay, Baschuk, Nikola, Hawkins, Christine J ORCID: 0000-0001-8120-1071, Johnston, Amelia J, Orian, Jacqueline Monique, Hoogenraad, Nicholas J, Poon, Ivan K ORCID: 0000-0002-9119-7173, Hill, Andrew F ORCID: 0000-0001-5581-2354, Jois, Markandeya ORCID: 0000-0002-0636-066X, Timpson, P, Parker, Belinda S and Mathivanan, Suresh ORCID: 0000-0002-7290-5795 (2021) Oral administration of bovine milk-derived extracellular vesicles induces senescence in the primary tumor but accelerates cancer metastasis. Nature Communications, 12. ISSN 2041-1723


The concept that extracellular vesicles (EVs) from the diet can be absorbed by the intestinal tract of the consuming organism, be bioavailable in various organs, and in-turn exert phenotypic changes is highly debatable. Here, we isolate EVs from both raw and commercial bovine milk and characterize them by electron microscopy, nanoparticle tracking analysis, western blotting, quantitative proteomics and small RNA sequencing analysis. Orally administered bovine milk-derived EVs survive the harsh degrading conditions of the gut, in mice, and is subsequently detected in multiple organs. Milk-derived EVs orally administered to mice implanted with colorectal and breast cancer cells reduce the primary tumor burden. Intriguingly, despite the reduction in primary tumor growth, milk-derived EVs accelerate metastasis in breast and pancreatic cancer mouse models. Proteomic and biochemical analysis reveal the induction of senescence and epithelial-to-mesenchymal transition in cancer cells upon treatment with milk-derived EVs. Timing of EV administration is critical as oral administration after resection of the primary tumor reverses the pro-metastatic effects of milk-derived EVs in breast cancer models. Taken together, our study provides context-based and opposing roles of milk-derived EVs as metastasis inducers and suppressors.

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Item type Article
URI https://vuir.vu.edu.au/id/eprint/45307
DOI 10.1038/s41467-021-24273-8
Official URL https://www.nature.com/articles/s41467-021-24273-8
Subjects Current > FOR (2020) Classification > 3101 Biochemistry and cell biology
Current > FOR (2020) Classification > 3211 Oncology and carcinogenesis
Current > Division/Research > Chancellery
Keywords extracellular vesicles, diet, cancer, cancer metastasis, bovine milk, tumour growth
Citations in Scopus 42 - View on Scopus
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