Affiliation:
1. Cheeloo College of Medicine Shandong University Jinan China
2. Department of Oncology Maternal and Child Health Care Hospital of Zibo Zibo China
3. Department of Pathology Affiliated Hospital of Weifang Medical University Weifang China
4. Department of Medical Oncology Affiliated Hospital of Weifang Medical University Weifang China
5. Department of Pathology Weifang Medical University Weifang China
Abstract
AbstractBackgroundEmerging evidence has revealed that tumor‐associated macrophages (TAMs) and exosomes play a crucial role in the microenvironment for tumor growth. However, the mechanisms through which exosomal miRNAs modulate TAMs and tumor development in breast cancer are not fully understood.MethodsWe constructed a macrophage model and an indirect coculture system consist of breast cancer cells and macrophages. Exosomes were isolated from BC cells culture supernatant and identified by transmission electron microscopy, Western blot and Nanosight LM10 system. The expression of miR‐148b‐3p in exosomes was determined by qRT‐PCR and the effect of exosomal miR‐148b‐3p on macrophage polarization was measured using qRT‐PCR and ELISA. The proliferation, migration and invasion of BC cells were estimated by EdU, wound healing assay and transwell assay. We employed bioinformatics, luciferase reporter assay and Western blot to identify the target gene of miR‐148b‐3p. Western blot was used to clarify the mechanism of exosomal miR‐148b‐3p mediated the crosstalk between BC cells and M2 macrophages.ResultsCancer‐derived exosomes could induce M2 polarization of macrophages, which promoted the migration and invasion of breast cancer cells. We found that exosomal miR‐148b‐3p was overexpressed in breast cancer cell‐derived exosomes and correlated with lymph node metastasis, late tumor stage and worse prognosis. Upregulated miR‐148b‐3p expression in exosomes modulated macrophage polarization by targeting TSC2, which promoted the proliferation and might affect migration and invasion of breast cancer cells. Interestingly, we found that exosomal miR‐148b‐3p could induce M2 macrophage polarization via the TSC2/mTORC1 signaling pathway in breast cancer.ConclusionOverall, our study elucidated that miR‐148b‐3p could be transported by exosomes from breast cancer cells to surrounding macrophages and induced M2 polarization by targeting TSC2, providing novel insights for breast cancer therapy.
Funder
National Natural Science Foundation of China
Subject
Pulmonary and Respiratory Medicine,Oncology,General Medicine
Cited by
2 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献