Lactobacillus rhamnosus-derived extracellular vesicles influence calcium deposition in a model of breast cancer intraductal calcium stress

Summary: Extracellular calcium export by the breast ductal epithelium is crucial during lactation and plays a significant role in breast cancer progression. Intraductal calcium deposition is a hallmark of aggressive premalignant lesions. This study tested the hypothesis that microbiome-derived extra...

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Main Authors: Ngoc Vuong, Melany Alomia, Ahana Byne, Purva Gade, Thomas Raymond Philipson, Rayan Ibrahim Alhammad, Cade J. Skislak, Intisar Alruwaili, Fahad M. Alsaab, Weidong Zhou, Marissa Howard, Andrea Brothers, Amanda Haymond Still, Robyn P. Araujo, Monique Van Hoek, Barbara Birkaya, Virginia Espina, Richard A. Hoefer, Lance Liotta, Alessandra Luchini
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004225007990
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Summary:Summary: Extracellular calcium export by the breast ductal epithelium is crucial during lactation and plays a significant role in breast cancer progression. Intraductal calcium deposition is a hallmark of aggressive premalignant lesions. This study tested the hypothesis that microbiome-derived extracellular vesicles (EVs) influence calcium modulation in premalignant breast cancer lesions. Based on the analysis of plasma, serum, saliva, and tissue collected from breast cancer patients and controls (N = 150), Lactobacillus rhamnosus (Lr) was chosen as the model microbiota. In a BT-474 human breast cancer cell line monolayer culture under acute calcium stress, Lr EVs enhanced intracellular calcium intake. In a BT474 3D spheroid model under chronic calcium stress, Lr EVs increased extracellular calcium deposition and mRNA expression of calcium export channel plasma membrane calcium-transporting ATPase 2 (PMCA2) and stromal interaction molecule 1 (STIM1) in a dose-dependent manner. We propose that Lr EVs influence calcium regulation and mineral deposition, thereby affecting premalignant breast cancer progression.
ISSN:2589-0042