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循环细胞外囊泡中细胞外基质蛋白 1 的升高支持肥胖条件下乳腺癌的进展。

Elevated extracellular matrix protein 1 in circulating extracellular vesicles supports breast cancer progression under obesity conditions.

机构信息

Centre for Cancer & Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.

Hangzhou Xixi Hospital, Zhejiang Chinese Medical University, Hangzhou, China.

出版信息

Nat Commun. 2024 Feb 24;15(1):1685. doi: 10.1038/s41467-024-45995-5.

DOI:10.1038/s41467-024-45995-5
PMID:38402239
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10894219/
Abstract

The cargo content in small extracellular vesicles (sEVs) changes under pathological conditions. Our data shows that in obesity, extracellular matrix protein 1 (ECM1) protein levels are significantly increased in circulating sEVs, which is dependent on integrin-β2. Knockdown of integrin-β2 does not affect cellular ECM1 protein levels but significantly reduces ECM1 protein levels in the sEVs released by these cells. In breast cancer (BC), overexpressing ECM1 increases matrix metalloproteinase 3 (MMP3) and S100A/B protein levels. Interestingly, sEVs purified from high-fat diet-induced obesity mice (D-sEVs) deliver more ECM1 protein to BC cells compared to sEVs from control diet-fed mice. Consequently, BC cells secrete more ECM1 protein, which promotes cancer cell invasion and migration. D-sEVs treatment also significantly enhances ECM1-mediated BC metastasis and growth in mouse models, as evidenced by the elevated tumor levels of MMP3 and S100A/B. Our study reveals a mechanism and suggests sEV-based strategies for treating obesity-associated BC.

摘要

小细胞外囊泡（sEVs）中的货物内容在病理条件下发生变化。我们的数据表明，在肥胖症中，循环 sEVs 中的细胞外基质蛋白 1（ECM1）蛋白水平显著增加，这依赖于整合素-β2。整合素-β2 的敲低不会影响细胞内 ECM1 蛋白水平，但会显著降低这些细胞释放的 sEVs 中的 ECM1 蛋白水平。在乳腺癌（BC）中，过表达 ECM1 会增加基质金属蛋白酶 3（MMP3）和 S100A/B 蛋白水平。有趣的是，与来自对照饮食喂养小鼠的 sEVs 相比，从高脂肪饮食诱导肥胖小鼠（D-sEVs）中纯化的 sEVs 向 BC 细胞输送更多的 ECM1 蛋白。因此，BC 细胞分泌更多的 ECM1 蛋白，这促进了癌细胞的侵袭和迁移。D-sEVs 处理还显著增强了 ECM1 介导的 BC 转移和在小鼠模型中的生长，这可以通过 MMP3 和 S100A/B 的肿瘤水平升高来证明。我们的研究揭示了一种机制，并提出了基于 sEV 的策略来治疗肥胖相关的 BC。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e990/10894219/d14f85fd5bde/41467_2024_45995_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e990/10894219/c779bb3512dc/41467_2024_45995_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e990/10894219/579504c55d2f/41467_2024_45995_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e990/10894219/32f01b0b6394/41467_2024_45995_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e990/10894219/bb671bb6b3d9/41467_2024_45995_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e990/10894219/7ce7323fc4e1/41467_2024_45995_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e990/10894219/d14f85fd5bde/41467_2024_45995_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e990/10894219/c779bb3512dc/41467_2024_45995_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e990/10894219/579504c55d2f/41467_2024_45995_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e990/10894219/32f01b0b6394/41467_2024_45995_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e990/10894219/bb671bb6b3d9/41467_2024_45995_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e990/10894219/7ce7323fc4e1/41467_2024_45995_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e990/10894219/d14f85fd5bde/41467_2024_45995_Fig6_HTML.jpg

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