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

Keyang Xu, Ai Fu, Zhaoyi Li, Liangbin Miao, Zhonghan Lou, Keying Jiang, Condon Lau, Tao Su, Tiejun Tong, Jianfeng Bao (), Aiping Lyu () and Hiu Yee Kwan ()
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Keyang Xu: Hong Kong Baptist University
Ai Fu: Zhejiang Chinese Medical University
Zhaoyi Li: Zhejiang Chinese Medical University
Liangbin Miao: Zhejiang Chinese Medical University
Zhonghan Lou: Zhejiang Chinese Medical University
Keying Jiang: Hong Kong Baptist University
Condon Lau: City University of Hong Kong
Tao Su: Guangzhou University of Chinese Medicine
Tiejun Tong: Hong Kong Baptist University
Jianfeng Bao: Zhejiang Chinese Medical University
Aiping Lyu: Hong Kong Baptist University
Hiu Yee Kwan: Hong Kong Baptist University

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-45995-5

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