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

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-04-28 DOI:10.1016/j.isci.2025.112538

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

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引用次数: 0

Abstract

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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鼠李糖乳杆菌衍生的细胞外囊泡影响乳腺癌导管内钙应激模型中的钙沉积

乳腺导管上皮细胞外钙输出在哺乳期间至关重要，并在乳腺癌进展中起重要作用。导管内钙沉积是侵袭性癌前病变的标志。本研究验证了微生物来源的细胞外囊泡（EVs）影响乳腺癌癌前病变中钙调节的假设。通过对乳腺癌患者和对照组（N = 150）的血浆、血清、唾液和组织进行分析，选择鼠李糖乳杆菌（Lactobacillus rhamnosus, Lr）作为模型微生物群。在急性钙胁迫下的BT-474人乳腺癌细胞系单层培养中，Lr ev增加了细胞内钙的摄入。在慢性钙胁迫下的BT474三维球体模型中，Lr ev以剂量依赖性的方式增加了细胞外钙沉积和钙输出通道质膜钙转运atp酶2 （PMCA2）和基质相互作用分子1 （STIM1）的mRNA表达。我们提出Lr ev影响钙调节和矿物质沉积，从而影响癌前乳腺癌的进展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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