Bone marrow cells are differentiated into MDSCs by BCC‐Ex through down‐regulating the expression of CXCR4 and activating STAT3 signalling pathway
| العنوان: | Bone marrow cells are differentiated into MDSCs by BCC‐Ex through down‐regulating the expression of CXCR4 and activating STAT3 signalling pathway |
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| المؤلفون: | Hao-Cheng Gu, Quan-Wen Liu, Ke-Yu Deng, Hongbo Xin, Ling Xiao, Yong Chen, Guo-Si-Lang Zuo, Jing-Yuan Li, Jia-Le Zhao, Han-You Wu, Wen-Jie Zhang |
| المصدر: | Journal of Cellular and Molecular Medicine |
| بيانات النشر: | Wiley, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | STAT3 Transcription Factor, 0301 basic medicine, Receptors, CXCR4, T-Lymphocytes, MDSCs, Nitric Oxide Synthase Type II, Bone Marrow Cells, Breast Neoplasms, Spleen, exosomes, CXCR4, Proinflammatory cytokine, STAT3, Mice, 03 medical and health sciences, Chemokine receptor, breast cancer, 0302 clinical medicine, Tumor Microenvironment, medicine, Animals, Humans, Mice, Inbred BALB C, biology, Chemistry, Myeloid-Derived Suppressor Cells, Cell Differentiation, Original Articles, Cell Biology, 030104 developmental biology, medicine.anatomical_structure, Apoptosis, 030220 oncology & carcinogenesis, Cancer cell, Cancer research, biology.protein, Molecular Medicine, Original Article, Female, Bone marrow, Signal Transduction |
| الوصف: | Studies showed that the increase of myeloid‐derived suppressor cells (MDSCs) in tumour microenvironment is closely related to the resistant treatment and poor prognosis of metastatic breast cancer. However, the effect of tumour‐derived exosomes on MDSCs and its mechanism are not clear. Here, we reported that breast cancer cells (4T1)‐secreted exosomes (BCC‐Ex) were able to differentiate bone marrow cells into MDSCs and significantly inhibited the proliferation of T lymphocytes to provide an immunosuppressive microenvironment for cancer cells in vivo and in vitro. The number of MDSCs in bone marrow and spleen of 4T1 tumour‐bearing mice and BCC‐Ex infused mice was significantly higher than that of normal mice, whereas the number of T lymphocytes in spleen was significantly decreased. In addition, BCC‐Ex markedly promoted the differentiation of MDSCs from bone marrow cells or bone marrow cells derived macrophages, seen as the increased expressions of MDSCs‐related functional proteins Arginase‐1 (Arg‐1) and inducible nitric oxide synthase (iNOS). Furthermore, BCC‐Ex significantly down‐regulated the expressions of chemokine receptor CXCR4 and markedly up‐regulated the levels of inflammatory cytokines IL‐6 and IL‐10 in bone marrow cells and macrophages and remarkably inhibited the division and proliferation of T cells. Importantly, CXCR4 agonist, CXCL12, could reverse the function of BCC‐Ex, indicating that BCC‐Ex‐induced MDSCs might be dependent on the down‐regulation of CXCR4. Western blot showed that BCC‐Ex significantly promoted the phosphorylation of STAT3 in bone marrow cells, resulting in the inhibitions of the proliferation and apoptosis of bone marrow cells, and the aggravation of the differentiation of bone marrow cells into MDSCs. |
| تدمد: | 1582-4934 1582-1838 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5b038459d6e2eeb4b91ecae6f72186d0 https://doi.org/10.1111/jcmm.16559 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....5b038459d6e2eeb4b91ecae6f72186d0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15824934 15821838 |
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