Breast adipose tissue-derived extracellular vesicles from obese women alter tumor cell metabolism.

TitleBreast adipose tissue-derived extracellular vesicles from obese women alter tumor cell metabolism.
Publication TypeJournal Article
Year of Publication2023
AuthorsLiu S, Benito-Martin A, Vatter FAPelissie, Hanif SZ, Liu C, Bhardwaj P, Sethupathy P, Farghli AR, Piloco P, Paik P, Mushannen M, Dong X, Otterburn DM, Cohen L, Bareja R, Krumsiek J, Cohen-Gould L, Calto S, Spector JA, Elemento O, Lyden DC, Brown KA
JournalEMBO Rep
Date Published2023 Dec 06
KeywordsAdipose Tissue, Breast Neoplasms, Extracellular Vesicles, Female, Humans, MicroRNAs, Obesity, Proteins, Ribosomal Protein S6 Kinases, 70-kDa

Breast adipose tissue is an important contributor to the obesity-breast cancer link. Extracellular vesicles (EVs) are nanosized particles containing selective cargo, such as miRNAs, that act locally or circulate to distant sites to modulate target cell functions. Here, we find that long-term education of breast cancer cells with EVs obtained from breast adipose tissue of women who are overweight or obese (O-EVs) results in increased proliferation. RNA-seq analysis of O-EV-educated cells demonstrates increased expression of genes involved in oxidative phosphorylation, such as ATP synthase and NADH: ubiquinone oxidoreductase. O-EVs increase respiratory complex protein expression, mitochondrial density, and mitochondrial respiration in tumor cells. The mitochondrial complex I inhibitor metformin reverses O-EV-induced cell proliferation. Several miRNAs-miR-155-5p, miR-10a-3p, and miR-30a-3p-which promote mitochondrial respiration and proliferation, are enriched in O-EVs relative to EVs from lean women. O-EV-induced proliferation and mitochondrial activity are associated with stimulation of the Akt/mTOR/P70S6K pathway, and are reversed upon silencing of P70S6K. This study reveals a new facet of the obesity-breast cancer link with human breast adipose tissue-derived EVs causing metabolic reprogramming of breast cancer cells.

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Alternate JournalEMBO Rep
PubMed ID37929643
PubMed Central IDPMC10702795
Grant ListT32 GM007739 / GM / NIGMS NIH HHS / United States
R01 CA215797 / CA / NCI NIH HHS / United States

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