Tumor-associated macrophages-mediated CXCL8 infiltration enhances breast cancer metastasis: Suppression by Danirixin
| Autor: | Haibo Wang, Xiangbo Cao, Meng Lv, Chen Liu, Yan Mao, Yongmei Wang, Zhi-Dong Lv, Gang Nie |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Epithelial-Mesenchymal Transition medicine.medical_treatment Immunology Population Mice Nude Antineoplastic Agents Breast Neoplasms Cell Line Metastasis 03 medical and health sciences 0302 clinical medicine Breast cancer Piperidines Cell Movement Tumor-Associated Macrophages medicine Animals Humans Immunology and Allergy Sulfones Interleukin 8 CXC chemokine receptors skin and connective tissue diseases education Pharmacology Mice Inbred BALB C education.field_of_study Tumor microenvironment business.industry Interleukin-8 Cancer medicine.disease 030104 developmental biology Cytokine 030220 oncology & carcinogenesis Neoplastic Stem Cells Cancer research Female business |
| Zdroj: | International Immunopharmacology. 95:107153 |
| ISSN: | 1567-5769 |
| Popis: | Breast cancer is the most frequent cancer among females and the second most common cause of cancer deaths worldwide. Tumor-associated macrophages (TAMs) are the most abundant immune cell population in the tumor microenvironment, including breast cancer. Breast cancer stem cells (BCSCs) play an important role in regulating breast cancer growth and metastasis, which still remains an obstacle for successful treatment of breast cancer and requires further investigation, as well as the potential therapeutic strategies. Cytokine array validated that C-X-C motif chemokine ligand 8 (CXCL8) is a pivotal chemokine secreted by TAMs, and CXCL8 could enhance breast cancer migration, invasion ability, and epithelial-mesenchymal transition (EMT) in both animal and human breast cancer. In this study, the clinical data firstly indicated that high CXCL8 expression was significantly associated with metastasis and tumor growth in breast cancer patients. Then, we showed that TAMs-released CXCL8 could markedly elevate the migration, invasion and EMT events in breast cancer cells, as well as the self-renewal of BCSCs in vitro. These processes were markedly abrogated by the treatment of Danirixin, a reversible and selective antagonist of CXC chemokine receptor 2 (CXCR2). Consistently, the in vivo analysis confirmed that CXCL8 suppression using Danirixin effectively reduced the tumor growth, lung metastasis and repressed the self-renewal of BCSCs. Collectively, TAMs/CXCL8 could enhance BCSCs self-renewal and breast cancer metastasis, and these effects could be markedly abolished by Danirixin treatment, suppressing breast cancer progression consequently. Therefore, Danirixin could be considered as a novel and effective therapeutic strategy for breast cancer treatment without obvious toxicity to major organs. |
| Databáze: | OpenAIRE |
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