Elevated extracellular matrix protein 1 in circulating extracellular vesicles supports breast cancer progression under obesity conditions
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 d...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-45995-5 |
| _version_ | 1797273951742722048 |
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| author | Keyang Xu Ai Fu Zhaoyi Li Liangbin Miao Zhonghan Lou Keying Jiang Condon Lau Tao Su Tiejun Tong Jianfeng Bao Aiping Lyu Hiu Yee Kwan |
| author_facet | Keyang Xu Ai Fu Zhaoyi Li Liangbin Miao Zhonghan Lou Keying Jiang Condon Lau Tao Su Tiejun Tong Jianfeng Bao Aiping Lyu Hiu Yee Kwan |
| author_sort | Keyang Xu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T14:51:28Z |
| format | Article |
| id | doaj.art-5bdde1ac1f024822849733fcd0641e17 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-07T14:51:28Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-5bdde1ac1f024822849733fcd0641e172024-03-05T19:39:52ZengNature PortfolioNature Communications2041-17232024-02-0115111710.1038/s41467-024-45995-5Elevated extracellular matrix protein 1 in circulating extracellular vesicles supports breast cancer progression under obesity conditionsKeyang Xu0Ai Fu1Zhaoyi Li2Liangbin Miao3Zhonghan Lou4Keying Jiang5Condon Lau6Tao Su7Tiejun Tong8Jianfeng Bao9Aiping Lyu10Hiu Yee Kwan11Centre for Cancer & Inflammation Research, School of Chinese Medicine, Hong Kong Baptist UniversityHangzhou Xixi Hospital, Zhejiang Chinese Medical UniversityHangzhou Xixi Hospital, Zhejiang Chinese Medical UniversityHangzhou Xixi Hospital, Zhejiang Chinese Medical UniversityHangzhou Xixi Hospital, Zhejiang Chinese Medical UniversityCentre for Cancer & Inflammation Research, School of Chinese Medicine, Hong Kong Baptist UniversityDepartment of Physics, City University of Hong KongInternational Institute for Translational Chinese Medicine, School of Pharmaceutical Science, Guangzhou University of Chinese MedicineDepartment of Mathematics, Hong Kong Baptist UniversityHangzhou Xixi Hospital, Zhejiang Chinese Medical UniversityCentre for Cancer & Inflammation Research, School of Chinese Medicine, Hong Kong Baptist UniversityCentre for Cancer & Inflammation Research, School of Chinese Medicine, Hong Kong Baptist UniversityAbstract 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.https://doi.org/10.1038/s41467-024-45995-5 |
| spellingShingle | Keyang Xu Ai Fu Zhaoyi Li Liangbin Miao Zhonghan Lou Keying Jiang Condon Lau Tao Su Tiejun Tong Jianfeng Bao Aiping Lyu Hiu Yee Kwan Elevated extracellular matrix protein 1 in circulating extracellular vesicles supports breast cancer progression under obesity conditions Nature Communications |
| title | Elevated extracellular matrix protein 1 in circulating extracellular vesicles supports breast cancer progression under obesity conditions |
| title_full | Elevated extracellular matrix protein 1 in circulating extracellular vesicles supports breast cancer progression under obesity conditions |
| title_fullStr | Elevated extracellular matrix protein 1 in circulating extracellular vesicles supports breast cancer progression under obesity conditions |
| title_full_unstemmed | Elevated extracellular matrix protein 1 in circulating extracellular vesicles supports breast cancer progression under obesity conditions |
| title_short | Elevated extracellular matrix protein 1 in circulating extracellular vesicles supports breast cancer progression under obesity conditions |
| title_sort | elevated extracellular matrix protein 1 in circulating extracellular vesicles supports breast cancer progression under obesity conditions |
| url | https://doi.org/10.1038/s41467-024-45995-5 |
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