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

Monisha Samuel, Pamali Fonseka, Rahul Sanwlani, Lahiru Gangoda, Sing Ho Chee, Shivakumar Keerthikumar, Alex Spurling, Sai V. Chitti, Damien Zanker, Ching-Seng Ang, Ishara Atukorala, Taeyoung Kang, Sanjay Shahi, Akbar L. Marzan, Christina Nedeva, Claire Vennin, Morghan C. Lucas, Lesley Cheng, David Herrmann, Mohashin Pathan, David Chisanga, Sean C. Warren, Kening Zhao, Nidhi Abraham, Sushma Anand, Stephanie Boukouris, Christopher G. Adda, Lanzhou Jiang, Tanmay M. Shekhar, Nikola Baschuk, Christine J. Hawkins, Amelia J. Johnston, Jacqueline Monique Orian, Nicholas J. Hoogenraad, Ivan K. Poon, Andrew F. Hill, Markandeya Jois, Paul Timpson, Belinda S. Parker and Suresh Mathivanan ()
Additional contact information
Monisha Samuel: La Trobe University
Pamali Fonseka: La Trobe University
Rahul Sanwlani: La Trobe University
Lahiru Gangoda: La Trobe University
Sing Ho Chee: La Trobe University
Shivakumar Keerthikumar: La Trobe University
Alex Spurling: La Trobe University
Sai V. Chitti: La Trobe University
Damien Zanker: La Trobe University
Ching-Seng Ang: University of Melbourne
Ishara Atukorala: La Trobe University
Taeyoung Kang: La Trobe University
Sanjay Shahi: La Trobe University
Akbar L. Marzan: La Trobe University
Christina Nedeva: La Trobe University
Claire Vennin: University of New South Wales
Morghan C. Lucas: University of New South Wales
Lesley Cheng: La Trobe University
David Herrmann: University of New South Wales
Mohashin Pathan: La Trobe University
David Chisanga: La Trobe University
Sean C. Warren: University of New South Wales
Kening Zhao: La Trobe University
Nidhi Abraham: La Trobe University
Sushma Anand: La Trobe University
Stephanie Boukouris: La Trobe University
Christopher G. Adda: La Trobe University
Lanzhou Jiang: La Trobe University
Tanmay M. Shekhar: La Trobe University
Nikola Baschuk: La Trobe University
Christine J. Hawkins: La Trobe University
Amelia J. Johnston: La Trobe University
Jacqueline Monique Orian: La Trobe University
Nicholas J. Hoogenraad: La Trobe University
Ivan K. Poon: La Trobe University
Andrew F. Hill: La Trobe University
Markandeya Jois: La Trobe University
Paul Timpson: University of New South Wales
Belinda S. Parker: La Trobe University
Suresh Mathivanan: La Trobe University

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: Abstract 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24273-8

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DOI: 10.1038/s41467-021-24273-8

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