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Dexmedetomidine expands monocytic myeloid-derived suppressor cells and promotes tumour metastasis after lung cancer surgery
- Source :
- Journal of Translational Medicine, Journal of Translational Medicine, Vol 16, Iss 1, Pp 1-13 (2018)
- Publication Year :
- 2018
- Publisher :
- BioMed Central, 2018.
-
Abstract
- Background Dexmedetomidine (DEX) has been reported to promote tumour metastases. However the underlying mechanisms remain unclear. The purpose of this study was to investigate whether DEX promotes tumour metastasis by inducing myeloid-derived suppressor cells (MDSC) in the context of surgery. Methods DEX was given to lung cancer patients and its effects on expansion of monocytic MDSC (M-MDSC) were studied in the context of surgery. Spontaneous tumour metastasis was induced in C57BL/6 mice and the effects of DEX on M-MDSC expansion and metastasis formation were assessed. Results DEX increased CD11b+CD33+HLA-DR–CD14+ M-MDSC in lung cancer patients after thoractomy. DEX-induced M-MDSC, in addition to have immunosuppressive activity, were more efficient in producing VEGF. Expansion of M-MDSC by DEX involved α2-adrenergic receptor. Using an experimental tumour metastasis mouse model, we demonstrated that the numbers of metastases on lung surface and CD11b+Ly6ChighLy6G− M-MDSC during postoperative period were enhanced in DEX-treated mice. Promotion of tumour metastasis by DEX-induced M-MDSC involved VEGF, a key factor for tumour angiogenesis. Conclusions DEX induces the proliferation of M-MDSC during postoperative period in lung cancer patients and this cell population is qualified with potent proangiogenic ability. Treatment of mice with DEX expands M-MDSC and promotes tumour metastasis through the increasing production of VEGF. Electronic supplementary material The online version of this article (10.1186/s12967-018-1727-9) contains supplementary material, which is available to authorized users.
- Subjects :
- 0301 basic medicine
Male
Vascular Endothelial Growth Factor A
Lung Neoplasms
CD33
Cell
lcsh:Medicine
Monocytes
Metastasis
0302 clinical medicine
polycyclic compounds
Medicine
Neoplasm Metastasis
Lung cancer surgery
education.field_of_study
Neovascularization, Pathologic
General Medicine
Middle Aged
medicine.anatomical_structure
030220 oncology & carcinogenesis
Female
Lung cancer
hormones, hormone substitutes, and hormone antagonists
Dexmedetomidine
Immunosuppressive Agents
endocrine system
Population
Context (language use)
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
Receptors, Adrenergic, alpha-2
Cell Line, Tumor
Animals
Humans
education
Aged
Cell Proliferation
business.industry
Research
Myeloid-Derived Suppressor Cells
lcsh:R
medicine.disease
Mice, Inbred C57BL
030104 developmental biology
Myeloid-derived Suppressor Cell
Cancer research
business
Perioperative care
Subjects
Details
- Language :
- English
- ISSN :
- 14795876
- Volume :
- 16
- Database :
- OpenAIRE
- Journal :
- Journal of Translational Medicine
- Accession number :
- edsair.doi.dedup.....6d7b5a86d97060c35416a20fcdf32822