Non–small cell lung cancer-derived exosomes promote proliferation, phagocytosis, and secretion of microglia via exosomal microRNA in the metastatic microenvironment
Non–small cell lung cancer (NSCLC) is the most common tumor that metastasizes to the brain. It is now accepted that the successful colonization and growth of tumor cells are determined by the interaction between tumor cells and the tumor microenvironment (TME). Microglia, brain innate immune cells,...
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Elsevier
2023-01-01
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Series: | Translational Oncology |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523322002534 |
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author | Peng Chen Ying Li Rui Liu Yi Xie Yu Jin Minghuan Wang Zhiyuan Yu Wei Wang Xiang Luo |
author_facet | Peng Chen Ying Li Rui Liu Yi Xie Yu Jin Minghuan Wang Zhiyuan Yu Wei Wang Xiang Luo |
author_sort | Peng Chen |
collection | DOAJ |
description | Non–small cell lung cancer (NSCLC) is the most common tumor that metastasizes to the brain. It is now accepted that the successful colonization and growth of tumor cells are determined by the interaction between tumor cells and the tumor microenvironment (TME). Microglia, brain innate immune cells, have been reported to play a vital role in the establishment of brain metastases. As essential mediators of intercellular communications, tumor-derived exosomes have an important role in the pathogenesis and progression of cancer by transferring their cargos to specific recipient cells. The crosstalk between microglia and tumor-derived exosomes has been extensively described. However, it is still unclear whether metastatic NSCLC cells secret exosomes to microglia and regulate the microglial functions. Here, our results showed that microglia aggregated in the brain metastatic sites. Meanwhile, microglia could take up the exosomes derived from NSCLC cells, leading to alterations of microglial morphology and increased proliferation, phagocytosis, and release of inflammatory cytokines including interleukin-6, interleukin-8, and CXCL1. Further investigation indicated that miR1246 was the most enriched microRNA in NSCLC-derived exosomes and mediated the partial effects of exosomes on microglia. Notably, miR1246 was also upregulated in the plasmatic exosomes of NSCLC patients. These results offer a new insight into the impact of NSCLC-derived exosomes on microglia and provide a new potential biomarker for diagnosing NSCLC. |
first_indexed | 2024-04-12T02:13:10Z |
format | Article |
id | doaj.art-2293c8d1e2344e27a1a4bf89c8952c9b |
institution | Directory Open Access Journal |
issn | 1936-5233 |
language | English |
last_indexed | 2024-04-12T02:13:10Z |
publishDate | 2023-01-01 |
publisher | Elsevier |
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series | Translational Oncology |
spelling | doaj.art-2293c8d1e2344e27a1a4bf89c8952c9b2022-12-22T03:52:19ZengElsevierTranslational Oncology1936-52332023-01-0127101594Non–small cell lung cancer-derived exosomes promote proliferation, phagocytosis, and secretion of microglia via exosomal microRNA in the metastatic microenvironmentPeng Chen0Ying Li1Rui Liu2Yi Xie3Yu Jin4Minghuan Wang5Zhiyuan Yu6Wei Wang7Xiang Luo8Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Correspondence author.Non–small cell lung cancer (NSCLC) is the most common tumor that metastasizes to the brain. It is now accepted that the successful colonization and growth of tumor cells are determined by the interaction between tumor cells and the tumor microenvironment (TME). Microglia, brain innate immune cells, have been reported to play a vital role in the establishment of brain metastases. As essential mediators of intercellular communications, tumor-derived exosomes have an important role in the pathogenesis and progression of cancer by transferring their cargos to specific recipient cells. The crosstalk between microglia and tumor-derived exosomes has been extensively described. However, it is still unclear whether metastatic NSCLC cells secret exosomes to microglia and regulate the microglial functions. Here, our results showed that microglia aggregated in the brain metastatic sites. Meanwhile, microglia could take up the exosomes derived from NSCLC cells, leading to alterations of microglial morphology and increased proliferation, phagocytosis, and release of inflammatory cytokines including interleukin-6, interleukin-8, and CXCL1. Further investigation indicated that miR1246 was the most enriched microRNA in NSCLC-derived exosomes and mediated the partial effects of exosomes on microglia. Notably, miR1246 was also upregulated in the plasmatic exosomes of NSCLC patients. These results offer a new insight into the impact of NSCLC-derived exosomes on microglia and provide a new potential biomarker for diagnosing NSCLC.http://www.sciencedirect.com/science/article/pii/S1936523322002534Brain metastasesNon–small cell lung cancerMicrogliaExosomesmiR1246 |
spellingShingle | Peng Chen Ying Li Rui Liu Yi Xie Yu Jin Minghuan Wang Zhiyuan Yu Wei Wang Xiang Luo Non–small cell lung cancer-derived exosomes promote proliferation, phagocytosis, and secretion of microglia via exosomal microRNA in the metastatic microenvironment Translational Oncology Brain metastases Non–small cell lung cancer Microglia Exosomes miR1246 |
title | Non–small cell lung cancer-derived exosomes promote proliferation, phagocytosis, and secretion of microglia via exosomal microRNA in the metastatic microenvironment |
title_full | Non–small cell lung cancer-derived exosomes promote proliferation, phagocytosis, and secretion of microglia via exosomal microRNA in the metastatic microenvironment |
title_fullStr | Non–small cell lung cancer-derived exosomes promote proliferation, phagocytosis, and secretion of microglia via exosomal microRNA in the metastatic microenvironment |
title_full_unstemmed | Non–small cell lung cancer-derived exosomes promote proliferation, phagocytosis, and secretion of microglia via exosomal microRNA in the metastatic microenvironment |
title_short | Non–small cell lung cancer-derived exosomes promote proliferation, phagocytosis, and secretion of microglia via exosomal microRNA in the metastatic microenvironment |
title_sort | non small cell lung cancer derived exosomes promote proliferation phagocytosis and secretion of microglia via exosomal microrna in the metastatic microenvironment |
topic | Brain metastases Non–small cell lung cancer Microglia Exosomes miR1246 |
url | http://www.sciencedirect.com/science/article/pii/S1936523322002534 |
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