TY - JOUR
T1 - Elevated extracellular matrix protein 1 in circulating extracellular vesicles supports breast cancer progression under obesity conditions
AU - Xu, Keyang
AU - Fu, Ai
AU - Li, Zhaoyi
AU - Miao, Liangbin
AU - Lou, Zhonghan
AU - Jiang, Keying
AU - Lau, Condon
AU - Su, Tao
AU - Tong, Tiejun
AU - Bao, Jianfeng
AU - Lu, Aiping
AU - Kwan, Hiu Yee
N1 - This work was partially supported by HMRF (08193596), FNRA-IG (RC-FNRA-IG/20-21/SCM/01), Shenzhen Basic Research Program for Shenzhen Virtual University Park (2021Szvup131), GDNSF (2021A1515010655 and 2023A1515011811) and ITC (PRP/015/19FX) to HY Kwan; Project of Hangzhou Science and Technology Bureau (20201203B179, 2021WJCY061, 2021WJCY186) and Project of Zhejiang Provincial Department of Health (2022KY1019) to JF Bao.
PY - 2024/2/24
Y1 - 2024/2/24
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85185954113&partnerID=8YFLogxK
U2 - 10.1038/s41467-024-45995-5
DO - 10.1038/s41467-024-45995-5
M3 - Journal article
SN - 2041-1723
VL - 15
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1685
ER -
