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 Lu*, Hiu Yee Kwan*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

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.
Original languageEnglish
Article number1685
Number of pages17
JournalNature Communications
Volume15
Issue number1
DOIs
Publication statusPublished - 24 Feb 2024

Scopus Subject Areas

  • Physics and Astronomy(all)
  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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