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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author 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
author_facet 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
author_sort Ngoc Vuong
collection DOAJ
description 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.
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spelling doaj-art-75de79ac8f55483fba11f0fa10a068fe2025-08-20T03:47:32ZengElsevieriScience2589-00422025-06-0128611253810.1016/j.isci.2025.112538Lactobacillus rhamnosus-derived extracellular vesicles influence calcium deposition in a model of breast cancer intraductal calcium stressNgoc Vuong0Melany Alomia1Ahana Byne2Purva Gade3Thomas Raymond Philipson4Rayan Ibrahim Alhammad5Cade J. Skislak6Intisar Alruwaili7Fahad M. Alsaab8Weidong Zhou9Marissa Howard10Andrea Brothers11Amanda Haymond Still12Robyn P. Araujo13Monique Van Hoek14Barbara Birkaya15Virginia Espina16Richard A. Hoefer17Lance Liotta18Alessandra Luchini19Center for Applied Proteomics and Molecular Medicine, George Mason University, 10920 George Mason Circle, MSN 1A9, Manassas, VA 20110, USACenter for Applied Proteomics and Molecular Medicine, George Mason University, 10920 George Mason Circle, MSN 1A9, Manassas, VA 20110, USACenter for Applied Proteomics and Molecular Medicine, George Mason University, 10920 George Mason Circle, MSN 1A9, Manassas, VA 20110, USACenter for Applied Proteomics and Molecular Medicine, George Mason University, 10920 George Mason Circle, MSN 1A9, Manassas, VA 20110, USACenter for Applied Proteomics and Molecular Medicine, George Mason University, 10920 George Mason Circle, MSN 1A9, Manassas, VA 20110, USACenter for Applied Proteomics and Molecular Medicine, George Mason University, 10920 George Mason Circle, MSN 1A9, Manassas, VA 20110, USA; Clinical Laboratory Department, College of Applied Medical Science, King Saud bin Abdulaziz University for Health Sciences, Al Ahsa, Saudi Arabia; King Abdullah International Medical Research Center, Al Ahsa, Saudi ArabiaCenter for Applied Proteomics and Molecular Medicine, George Mason University, 10920 George Mason Circle, MSN 1A9, Manassas, VA 20110, USASchool of Systems Biology, George Mason University, 10920 George Mason Circle, MSN 1A9, Manassas, VA 20110, USASchool of Systems Biology, George Mason University, 10920 George Mason Circle, MSN 1A9, Manassas, VA 20110, USA; College of Applied Medical Sciences, King Saud Bin Abdulaziz University for Health Sciences, Al Ahsa, Saudi ArabiaCenter for Applied Proteomics and Molecular Medicine, George Mason University, 10920 George Mason Circle, MSN 1A9, Manassas, VA 20110, USACenter for Applied Proteomics and Molecular Medicine, George Mason University, 10920 George Mason Circle, MSN 1A9, Manassas, VA 20110, USACollege Dean’s Office, American University, 4400 Massachusetts Avenue, Washington, DC 20016, USACenter for Applied Proteomics and Molecular Medicine, George Mason University, 10920 George Mason Circle, MSN 1A9, Manassas, VA 20110, USAThe University of Melbourne, Grattan Street, Parkville, VIC 3010, AustraliaSchool of Systems Biology, George Mason University, 10920 George Mason Circle, MSN 1A9, Manassas, VA 20110, USACenter for Applied Proteomics and Molecular Medicine, George Mason University, 10920 George Mason Circle, MSN 1A9, Manassas, VA 20110, USACenter for Applied Proteomics and Molecular Medicine, George Mason University, 10920 George Mason Circle, MSN 1A9, Manassas, VA 20110, USADorothy G. Hoefer Comprehensive Breast Center, 11803 Jefferson Avenue, Suite 130, Newport News, VA 23606, USACenter for Applied Proteomics and Molecular Medicine, George Mason University, 10920 George Mason Circle, MSN 1A9, Manassas, VA 20110, USACenter for Applied Proteomics and Molecular Medicine, George Mason University, 10920 George Mason Circle, MSN 1A9, Manassas, VA 20110, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004225007990Molecular biologyMicrobiologyCell biologyCancer
spellingShingle 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
Lactobacillus rhamnosus-derived extracellular vesicles influence calcium deposition in a model of breast cancer intraductal calcium stress
iScience
Molecular biology
Microbiology
Cell biology
Cancer
title Lactobacillus rhamnosus-derived extracellular vesicles influence calcium deposition in a model of breast cancer intraductal calcium stress
title_full Lactobacillus rhamnosus-derived extracellular vesicles influence calcium deposition in a model of breast cancer intraductal calcium stress
title_fullStr Lactobacillus rhamnosus-derived extracellular vesicles influence calcium deposition in a model of breast cancer intraductal calcium stress
title_full_unstemmed Lactobacillus rhamnosus-derived extracellular vesicles influence calcium deposition in a model of breast cancer intraductal calcium stress
title_short Lactobacillus rhamnosus-derived extracellular vesicles influence calcium deposition in a model of breast cancer intraductal calcium stress
title_sort lactobacillus rhamnosus derived extracellular vesicles influence calcium deposition in a model of breast cancer intraductal calcium stress
topic Molecular biology
Microbiology
Cell biology
Cancer
url http://www.sciencedirect.com/science/article/pii/S2589004225007990
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