Bio21 - Research Publications

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Author: Ang, Ching-Seng × Author: Chisanga, David × Author: Keerthikumar, Shivakumar ×

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    Oral administration of bovine milk-derived extracellular vesicles induces senescence in the primary tumor but accelerates cancer metastasis
    Samuel, M ; Fonseka, P ; Sanwlani, R ; Gangoda, L ; Chee, SH ; Keerthikumar, S ; Spurling, A ; Chitti, SV ; Zanker, D ; Ang, C-S ; Atukorala, I ; Kang, T ; Shahi, S ; Marzan, AL ; Nedeva, C ; Vennin, C ; Lucas, MC ; Cheng, L ; Herrmann, D ; Pathan, M ; Chisanga, D ; Warren, SC ; Zhao, K ; Abraham, N ; Anand, S ; Boukouris, S ; Adda, CG ; Jiang, L ; Shekhar, TM ; Baschuk, N ; Hawkins, CJ ; Johnston, AJ ; Orian, JM ; Hoogenraad, NJ ; Poon, IK ; Hill, AF ; Jois, M ; Timpson, P ; Parker, BS ; Mathivanan, S (NATURE RESEARCH, 2021-06-24)
    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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    Extracellular vesicles secreted by Saccharomyces cerevisiae are involved in cell wall remodelling
    Zhao, K ; Bleackley, M ; Chisanga, D ; Gangoda, L ; Fonseka, P ; Liem, M ; Kalra, H ; Al Saffar, H ; Keerthikumar, S ; Ang, C-S ; Adda, CG ; Jiang, L ; Yap, K ; Poon, IK ; Lock, P ; Bulone, V ; Anderson, M ; Mathivanan, S (NATURE PUBLISHING GROUP, 2019-08-09)
    Extracellular vesicles (EVs) are membranous vesicles that are released by cells. In this study, the role of the Endosomal Sorting Complex Required for Transport (ESCRT) machinery in the biogenesis of yeast EVs was examined. Knockout of components of the ESCRT machinery altered the morphology and size of EVs as well as decreased the abundance of EVs. In contrast, strains with deletions in cell wall biosynthesis genes, produced more EVs than wildtype. Proteomic analysis highlighted the depletion of ESCRT components and enrichment of cell wall remodelling enzymes, glucan synthase subunit Fks1 and chitin synthase Chs3, in yeast EVs. Interestingly, EVs containing Fks1 and Chs3 rescued the yeast cells from antifungal molecules. However, EVs from fks1∆ or chs3∆ or the vps23∆chs3∆ double knockout strain were unable to rescue the yeast cells as compared to vps23∆ EVs. Overall, we have identified a potential role for yeast EVs in cell wall remodelling.