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

Autor: Liu S; Department of Medicine, Weill Cornell Medicine, New York, NY, USA.; Department of Breast Surgery, The Second Hospital of Shandong University, Jinan, China., Benito-Martin A; Department of Medicine, Weill Cornell Medicine, New York, NY, USA.; Facultad de Medicina, Unidad de Investigación Biomédica, Universidad Alfonso X el Sabio (UAX), Madrid, Spain., Pelissier Vatter FA; Departments of Pediatrics and Cell and Developmental Biology, Weill Cornell Medicine, New York, NY, USA., Hanif SZ; Department of Medicine, Weill Cornell Medicine, New York, NY, USA., Liu C; Department of Medicine, Weill Cornell Medicine, New York, NY, USA., Bhardwaj P; Department of Medicine, Weill Cornell Medicine, New York, NY, USA., Sethupathy P; Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA., Farghli AR; Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA., Piloco P; Department of Medicine, Weill Cornell Medicine, New York, NY, USA., Paik P; Department of Medicine, Weill Cornell Medicine, New York, NY, USA., Mushannen M; Department of Medicine, Weill Cornell Medicine, New York, NY, USA.; Weill Cornell Medicine - Qatar, Doha, Qatar., Dong X; Department of Surgery, Weill Cornell Medicine, New York, NY, USA., Otterburn DM; Department of Surgery, Weill Cornell Medicine, New York, NY, USA., Cohen L; Department of Surgery, Weill Cornell Medicine, New York, NY, USA., Bareja R; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA., Krumsiek J; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA., Cohen-Gould L; Department of Biochemistry, Weill Cornell Medicine, New York, NY, USA.; Core Laboratories Center, Weill Cornell Medicine, New York, NY, USA., Calto S; Department of Cognitive Science, University of California San Diego, La Jolla, CA, USA., Spector JA; Department of Surgery, Weill Cornell Medicine, New York, NY, USA., Elemento O; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA., Lyden DC; Departments of Pediatrics and Cell and Developmental Biology, Weill Cornell Medicine, New York, NY, USA., Brown KA; Department of Medicine, Weill Cornell Medicine, New York, NY, USA.; Department of Cell Biology and Physiology, University of Kansas Medical Center, Kansas City, KS, USA.; University of Kansas Cancer Center, Kansas City, KS, USA.
Jazyk: angličtina
Zdroj: EMBO reports [EMBO Rep] 2023 Dec 06; Vol. 24 (12), pp. e57339. Date of Electronic Publication: 2023 Nov 06.
DOI: 10.15252/embr.202357339
Abstrakt: 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.
(© 2023 The Authors.)
Databáze: MEDLINE
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