PMID- 37551997 OWN - NLM STAT- MEDLINE DCOM- 20231023 LR - 20231024 IS - 2198-3844 (Electronic) IS - 2198-3844 (Linking) VI - 10 IP - 29 DP - 2023 Oct TI - The Interaction between Macrophages and Triple-negative Breast Cancer Cells Induces ROS-Mediated Interleukin 1alpha Expression to Enhance Tumorigenesis and Metastasis. PG - e2302857 LID - 10.1002/advs.202302857 [doi] LID - 2302857 AB - Triple-negative breast cancer (TNBC) has higher mortality than non-TNBC because of its stronger metastatic capacity. Increasing studies reported that TNBC tumors had more macrophage infiltration than non-TNBC tumors, which promoted the metastasis of TNBC cells. However, how TNBC cells become more malignant after interacting with macrophages is less reported. In this study, it is observed that when TNBC cells are co-cultured with macrophages, they display higher viability and stronger metastatic ability than non-TNBC cells. Mechanistic studies reveal that TNBC cells acquired these abilities via interactions with macrophages in three phases. First, within 12 h of co-culture with macrophages, some TNBC cells have significantly elevated levels of reactive oxygen species (ROS), which upregulate interleukin 1alpha (IL1alpha) expression in ERK1/2-c-Jun- and NF-kappaB-dependent manners at 24-48 h. Second, the secreted IL1alpha bound to IL1R1 activates the ERK1/2-ZEB1-VIM pathway which increases metastasis. Third, IL1alpha/IL1R1 facilitates its own synthesis and induces the expression of IL1beta and IL8 at 72-96 h through the MKK4-JNK-c-Jun and NF-kappaB signaling pathways. Moreover, a higher level of IL1alpha is positively correlated with more macrophage infiltration and shorter overall survival in breast cancer patients. Thus, reducing ROS elevation or downregulating IL1alpha expression can serve as new strategies to decrease metastasis of TNBC. CI - (c) 2023 The Authors. Advanced Science published by Wiley-VCH GmbH. FAU - Hao, Meng AU - Hao M AUID- ORCID: 0009-0002-0784-9376 AD - Department of Biomedical Sciences, Faculty of Health Sciences, University of Macau, Taipa, Macao SAR, 99078, China. FAU - Huang, Bin AU - Huang B AD - Department of Biomedical Sciences, Faculty of Health Sciences, University of Macau, Taipa, Macao SAR, 99078, China. FAU - Wu, Renfei AU - Wu R AD - Department of Biomedical Sciences, Faculty of Health Sciences, University of Macau, Taipa, Macao SAR, 99078, China. FAU - Peng, Zheng AU - Peng Z AD - Department of Biomedical Sciences, Faculty of Health Sciences, University of Macau, Taipa, Macao SAR, 99078, China. FAU - Luo, Kathy Qian AU - Luo KQ AUID- ORCID: 0000-0001-7454-9547 AD - Department of Biomedical Sciences, Faculty of Health Sciences, University of Macau, Taipa, Macao SAR, 99078, China. AD - Ministry of Education Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macao SAR, 99078, China. LA - eng GR - Faculty of Health Sciences/ GR - 068/2017/A2/Science and Technology Development Fund/ GR - 0147/2020/A3/Science and Technology Development Fund/ GR - 0004/2021/AKP/Science and Technology Development Fund/ GR - SP2021-00001-FSCPO/Ministry of Education Frontiers Science Centre for Precision Oncology, University of Macau/ GR - SP2023-00001-FSCPO/Ministry of Education Frontiers Science Centre for Precision Oncology, University of Macau/ PT - Journal Article DEP - 20230808 PL - Germany TA - Adv Sci (Weinh) JT - Advanced science (Weinheim, Baden-Wurttemberg, Germany) JID - 101664569 RN - 0 (NF-kappa B) RN - 0 (Reactive Oxygen Species) RN - 0 (Interleukin-1alpha) SB - IM MH - Humans MH - *NF-kappa B/metabolism MH - *Triple Negative Breast Neoplasms/pathology MH - Reactive Oxygen Species/metabolism MH - Interleukin-1alpha/metabolism MH - Cell Line, Tumor MH - Carcinogenesis/metabolism MH - Cell Transformation, Neoplastic MH - Macrophages/metabolism PMC - PMC10582438 OTO - NOTNLM OT - co-culture OT - interleukin 1alpha (IL1alpha) OT - macrophages OT - metastasis OT - reactive oxygen species (ROS) OT - triple-negative breast cancer (TNBC) COIS- The authors declare no conflict of interest. EDAT- 2023/08/08 12:41 MHDA- 2023/10/23 12:45 PMCR- 2023/08/08 CRDT- 2023/08/08 09:13 PHST- 2023/07/24 00:00 [revised] PHST- 2023/05/05 00:00 [received] PHST- 2023/10/23 12:45 [medline] PHST- 2023/08/08 12:41 [pubmed] PHST- 2023/08/08 09:13 [entrez] PHST- 2023/08/08 00:00 [pmc-release] AID - ADVS6271 [pii] AID - 10.1002/advs.202302857 [doi] PST - ppublish SO - Adv Sci (Weinh). 2023 Oct;10(29):e2302857. doi: 10.1002/advs.202302857. Epub 2023 Aug 8.