本研究旨在探讨脂肪因子白细胞介素（IL）-6促进三阴性乳腺癌（TNBC）五聚蛋白3（PTX3）表达的调节机制。我们建立了成熟脂肪细胞与TNBC细胞的体外共培养模型。 Transwell 系统。采用细胞划痕、Transwell迁移和基质侵袭实验评价TNBC细胞与脂肪细胞共培养的迁移和侵袭能力。接下来，我们利用慢病毒介导的功能缺失实验来研究PTX3在TNBC细胞脂肪细胞依赖性迁移中的作用。TNBC细胞与脂肪细胞共培养后，PTX3表达上调，伴随着细胞迁移和侵袭的增强。利用GEO数据和RNA-seq分析，我们确定PTX3是受脂肪TNBC微环境影响的关键靶基因。成熟脂肪细胞条件培养基和高脂饮食小鼠血清中IL-6的上调与这种效应相关，重组蛋白IL-6随着细胞内STAT3的磷酸化显着促进TNBC细胞的迁移和侵袭。和 PTX3 的上调。 PTX3 敲低抑制了 TNBC 细胞迁移并消除了与脂肪细胞共培养引起的迁移增强。此外，体内实验证实 PTX3 敲低可减少肥胖引起的肺转移。随后的细胞因子和药物抑制剂实验证实，脂肪细胞来源的IL-6通过激活STAT3信号通路促进PTX3表达。此外，生物信息学分析表明，PTX3 通过调节基质金属蛋白酶 (MMP) 家族促进 TNBC 转移。我们的研究阐明肥胖相关的代谢炎症通过 IL-6/STAT3/PTX3/MMP7 轴促进进展。版权所有 © 2024。出版者爱思唯尔有限公司

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.