Elevated extracellular matrix protein 1 in circulating extracellular vesicles supports breast cancer progression under obesity conditions.
Ke Yang XuAi FuZhaoyi LiLiangbin MiaoZhonghan LouKeying JiangCondon LauTao SuTie-Jun TongJianfeng BaoAi-Ping LuHiu Yee KwanPublished in: Nature communications (2024)
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.
Keyphrases
- extracellular matrix
- high fat diet induced
- insulin resistance
- protein protein
- metabolic syndrome
- induced apoptosis
- weight loss
- type diabetes
- amino acid
- binding protein
- oxidative stress
- adipose tissue
- cell proliferation
- cell death
- endoplasmic reticulum stress
- electronic health record
- young adults
- skeletal muscle
- smoking cessation
- replacement therapy