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Obesity-associated metabolic inflammation promotes triple-negative breast cancer progression through the interleukin-6/STAT3/pentraxin 3/matrix metalloproteinase 7 axis

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WOS体系：
Pubmed体系：

收录情况： ◇ SCIE

作者：
Xie Hailun[1,2,3,4] * ; Ruan Guotian[1,2,3,4] * ; Wei Lishuang[1,2,3,4] * ; Zhang Heyang[1,2,3,4] ; Shi Jinyu[1,2,3,4] ; Lin Shiqi[1,2,3,4] ; Liu Chenan[1,2,3,4] ; Liu Xiaoyue[1,2,3,4] ; Zheng Xin[1,2,3,4] ; Chen Yue[1,2,3,4] ; Deng Li[1,2,3,4] ; Shi Hanping[1,2,3,4] ;
机构： [1]Department of Gastrointestinal Surgery, Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, China [2]National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Beijing, China [3]Key Laboratory of Cancer FSMP for State Market Regulation, Beijing, China [4]Laboratory for Clinical Medicine, Capital Medical University, Beijing, China
出处：
DOI： 10.1016/j.intimp.2024.112332
ISSN：

关键词： Triple-negative breast cancer Tumor microenvironment Adipocytes Inflammation Obesity

摘要：
This study aimed to investigate the regulatory mechanism of the adipose factor interleukin (IL)-6 in promoting pentraxin 3 (PTX3) expression in triple-negative breast cancer (TNBC).We established an in vitro coculture model of mature adipocytes and TNBC cells using a Transwell system. Cell scratch, Transwell migration, and matrix invasion assays were used to evaluate the migration and invasion abilities of TNBC cells cocultured with adipocytes. Next, we used lentivirus-mediated functional depletion experiments to study PTX3's role in the adipocyte-dependent migration of TNBC cells.After coculturing TNBC cells with adipocytes, PTX3 expression was upregulated, which accompanied enhanced cell migration and invasion. Using GEO data and RNA-seq analysis, we identified PTX3 as a key target gene influenced by the adipose TNBC microenvironment. IL-6 upregulation in the conditioned medium of mature adipocytes and in the serum of high-fat diet mice was associated with this effect, and the recombinant protein IL-6 significantly promoted the migration and invasion of TNBC cells along with the phosphorylation of intracellular STAT3 and the upregulation of PTX3. PTX3 knockdown inhibited TNBC cell migration and eliminated the enhanced migration caused by coculturing with adipocytes. Furthermore, in vivo experiments confirmed that the PTX3 knockdown reduced obesity-induced lung metastasis. Subsequent experiments with cytokines and drug inhibitors confirmed that adipocyte-derived IL-6 promoted PTX3 expression by activating the STAT3 signaling pathway. Additionally, bioinformatic analysis indicated that PTX3 promotes TNBC metastasis by regulating the matrix metalloproteinase (MMP) family.Our study elucidated Obesity-related metabolic inflammation promotes the progression via the IL-6/STAT3/PTX3/MMP7 axis.Copyright © 2024. Published by Elsevier B.V.

基金：
Young Elite Scientists Sponsorship Program by CAST (2022QNRC001) and the National Key Research and Development Program (No. 2022YFC2009600).
语种：
外文
被引次数：
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2023]版：
大类 | 2 区 医学
小类 | 2 区 免疫学 2 区 药学
最新[2023]版：
大类 | 2 区 医学
小类 | 2 区 免疫学 2 区 药学
JCR分区：
出版当年[2022]版：
Q1 PHARMACOLOGY & PHARMACY Q2 IMMUNOLOGY
最新[2023]版：
Q1 PHARMACOLOGY & PHARMACY Q2 IMMUNOLOGY

影响因子： 最新[2023版] 最新五年平均 出版当年[2022版] 出版当年五年平均 出版前一年[2021版] 出版后一年[2023版]

第一作者：
第一作者机构： [1]Department of Gastrointestinal Surgery, Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, China [2]National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Beijing, China [3]Key Laboratory of Cancer FSMP for State Market Regulation, Beijing, China [4]Laboratory for Clinical Medicine, Capital Medical University, Beijing, China
共同第一作者：
通讯作者：
通讯机构： [1]Department of Gastrointestinal Surgery, Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, China [2]National Clinical Research Center for Geriatric Diseases, Xuanwu Hospital, Capital Medical University, Beijing, China [3]Key Laboratory of Cancer FSMP for State Market Regulation, Beijing, China [4]Laboratory for Clinical Medicine, Capital Medical University, Beijing, China
推荐引用方式(GB/T 7714)：
Xie Hailun,Ruan Guotian,Wei Lishuang,et al.Obesity-associated metabolic inflammation promotes triple-negative breast cancer progression through the interleukin-6/STAT3/pentraxin 3/matrix metalloproteinase 7 axis[J].International Immunopharmacology.2024,136:112332.doi:10.1016/j.intimp.2024.112332.
APA：
Xie Hailun,Ruan Guotian,Wei Lishuang,Zhang Heyang,Shi Jinyu...&Shi Hanping.(2024).Obesity-associated metabolic inflammation promotes triple-negative breast cancer progression through the interleukin-6/STAT3/pentraxin 3/matrix metalloproteinase 7 axis.International Immunopharmacology,136,
MLA：
Xie Hailun,et al."Obesity-associated metabolic inflammation promotes triple-negative breast cancer progression through the interleukin-6/STAT3/pentraxin 3/matrix metalloproteinase 7 axis".International Immunopharmacology 136.(2024):112332

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