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Endometrial Cancer Cells Promote M2-Like Macrophage Polarization by Delivering Exosomal miRNA-21 under Hypoxia Condition
- Source :
- Journal of Immunology Research, Vol 2020 (2020), Journal of Immunology Research
- Publication Year :
- 2020
- Publisher :
- Hindawi Limited, 2020.
-
Abstract
- Increasing evidence has demonstrated that hypoxia was an aggressive feature in endometrial cancer (EC), which is significantly associated with the tumor grade, lymph node metastasis, and tumor resistance to chemotherapy. However, the relationship between hypoxia and the immune microenvironment in EC is not very clear. Exosomes are small membrane vesicles secreted from a variety of cell types which mediate cell-to-cell communication through transported biomolecules. Here, we investigated whether exosomes can play an immunomodulatory role in intercellular communication between EC cells and macrophages. EC KEL cells were cultured under hypoxia or normoxic condition to collect exosomes. After identification, the exosomes derived from hypoxic or normoxic KEL cells were cultured with the monocyte cell line THP-1 to study the immunoregulation function of KEL cells. The results showed that the total number of exosomes produced by hypoxic KEL cells was significantly higher than that in normoxic condition. In addition, hypoxia markedly stimulated the increase in miRNA-21 expression in the exosomes. After coculture, we found that exosomal miRNA-21 could be horizontally transferred into THP-1 cells. And then, the notably enhanced mRNA expression levels of IL-10 and CD206 in THP-1 cells were observed, suggestive of M2 polarization. To further study the effect of miRNA-21-containing exosomes, we transfected miRNA-21 mimics or inhibitor into THP-1 cells. The results showed that miRNA-21 mimics promoted IL-10 and CD206 mRNA expression levels, and the miRNA-21 inhibitor significantly prevented the alteration induced by intake of hypoxic KEL cell-derived exosomes. In summary, we found that endometrial cancer KEL cells in hypoxic condition promoted monocyte THP-1 cell transformation to M2-like polarization macrophages through delivering exosomal miRNA-21, which may be a potential mechanism of the formation of the immune microenvironment in EC progression.
- Subjects :
- Cell type
Article Subject
THP-1 Cells
Immunology
Cell
Macrophage polarization
Exosomes
03 medical and health sciences
0302 clinical medicine
Th2 Cells
Cell Movement
Cell Line, Tumor
medicine
Tumor Microenvironment
Immunology and Allergy
Humans
Hypoxia
030304 developmental biology
0303 health sciences
Chemistry
Monocyte
Macrophages
Cell Differentiation
General Medicine
Transfection
Hypoxia (medical)
Macrophage Activation
RC581-607
Microvesicles
Coculture Techniques
Endometrial Neoplasms
MicroRNAs
medicine.anatomical_structure
Cell Transformation, Neoplastic
Cell culture
030220 oncology & carcinogenesis
Cancer research
Cytokines
Female
medicine.symptom
Immunologic diseases. Allergy
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 23147156 and 23148861
- Volume :
- 2020
- Database :
- OpenAIRE
- Journal :
- Journal of Immunology Research
- Accession number :
- edsair.doi.dedup.....9f03988a15bb1d12d7bdbacc91950657