PMID- 38402239
OWN - NLM
STAT- MEDLINE
DCOM- 20240226
LR  - 20240227
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 15
IP  - 1
DP  - 2024 Feb 24
TI  - Elevated extracellular matrix protein 1 in circulating extracellular vesicles 
      supports breast cancer progression under obesity conditions.
PG  - 1685
LID - 10.1038/s41467-024-45995-5 [doi]
LID - 1685
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-beta2. Knockdown of integrin-beta2 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.
CI  - (c) 2024. The Author(s).
FAU - Xu, Keyang
AU  - Xu K
AUID- ORCID: 0000-0002-7049-2528
AD  - Centre for Cancer & Inflammation Research, School of Chinese Medicine, Hong Kong 
      Baptist University, Hong Kong, China.
FAU - Fu, Ai
AU  - Fu A
AD  - Hangzhou Xixi Hospital, Zhejiang Chinese Medical University, Hangzhou, China.
FAU - Li, Zhaoyi
AU  - Li Z
AD  - Hangzhou Xixi Hospital, Zhejiang Chinese Medical University, Hangzhou, China.
FAU - Miao, Liangbin
AU  - Miao L
AD  - Hangzhou Xixi Hospital, Zhejiang Chinese Medical University, Hangzhou, China.
FAU - Lou, Zhonghan
AU  - Lou Z
AD  - Hangzhou Xixi Hospital, Zhejiang Chinese Medical University, Hangzhou, China.
FAU - Jiang, Keying
AU  - Jiang K
AD  - Centre for Cancer & Inflammation Research, School of Chinese Medicine, Hong Kong 
      Baptist University, Hong Kong, China.
FAU - Lau, Condon
AU  - Lau C
AD  - Department of Physics, City University of Hong Kong, Hong Kong, China.
FAU - Su, Tao
AU  - Su T
AD  - International Institute for Translational Chinese Medicine, School of 
      Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, 
      China.
FAU - Tong, Tiejun
AU  - Tong T
AUID- ORCID: 0000-0003-0947-3990
AD  - Department of Mathematics, Hong Kong Baptist University, Hong Kong, China.
FAU - Bao, Jianfeng
AU  - Bao J
AD  - Hangzhou Xixi Hospital, Zhejiang Chinese Medical University, Hangzhou, China. 
      zjbjf1972@aliyun.com.
FAU - Lyu, Aiping
AU  - Lyu A
AUID- ORCID: 0000-0002-2303-0494
AD  - Centre for Cancer & Inflammation Research, School of Chinese Medicine, Hong Kong 
      Baptist University, Hong Kong, China. aipinglu@hkbu.edu.hk.
AD  - Institute of Systems Medicine and Health Sciences, Hong Kong Baptist University, 
      Hong Kong, China. aipinglu@hkbu.edu.hk.
FAU - Kwan, Hiu Yee
AU  - Kwan HY
AUID- ORCID: 0000-0002-6088-7323
AD  - Centre for Cancer & Inflammation Research, School of Chinese Medicine, Hong Kong 
      Baptist University, Hong Kong, China. hykwan@hkbu.edu.hk.
AD  - Institute of Systems Medicine and Health Sciences, Hong Kong Baptist University, 
      Hong Kong, China. hykwan@hkbu.edu.hk.
AD  - Institute of Research and Continuing Education, Hong Kong Baptist University, 
      Shenzhen, China. hykwan@hkbu.edu.hk.
LA  - eng
GR  - 08193596/Food and Health Bureau of the Government of the Hong Kong Special 
      Administrative Region | Health and Medical Research Fund (HMRF)/
GR  - RC-FNRA-IG/20-21/SCM/01/Hong Kong Baptist University (HKBU)/
GR  - RC-FNRA-IG/20-21/SCM/01/Hong Kong Baptist University (HKBU)/
GR  - 2021Szvup131/Shenzhen Science and Technology Innovation Commission/
GR  - 20201203B179/Hangzhou Science and Technology Bureau/
GR  - 2021WJCY061/Hangzhou Science and Technology Bureau/
GR  - 2021WJCY186/Changzhou Science and Technology Bureau (CZST)/
PT  - Journal Article
DEP - 20240224
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (Extracellular Matrix Proteins)
RN  - 0 (Integrins)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - 0 (Ecm1 protein, mouse)
SB  - IM
MH  - Animals
MH  - Mice
MH  - Extracellular Matrix Proteins/metabolism
MH  - *Extracellular Vesicles/metabolism
MH  - Integrins
MH  - Matrix Metalloproteinase 3/genetics
MH  - *Neoplasms
MH  - Obesity
PMC - PMC10894219
COIS- The authors declare no competing interests.
EDAT- 2024/02/25 00:42
MHDA- 2024/02/26 06:44
PMCR- 2024/02/24
CRDT- 2024/02/24 23:19
PHST- 2023/03/24 00:00 [received]
PHST- 2024/02/06 00:00 [accepted]
PHST- 2024/02/26 06:44 [medline]
PHST- 2024/02/25 00:42 [pubmed]
PHST- 2024/02/24 23:19 [entrez]
PHST- 2024/02/24 00:00 [pmc-release]
AID - 10.1038/s41467-024-45995-5 [pii]
AID - 45995 [pii]
AID - 10.1038/s41467-024-45995-5 [doi]
PST - epublish
SO  - Nat Commun. 2024 Feb 24;15(1):1685. doi: 10.1038/s41467-024-45995-5.