Dexmedetomidine expands monocytic myeloid-derived suppressor cells and promotes tumour metastasis after lung cancer surgery

• Published in: Journal of translational medicine 2018-12, Vol.16 (1), p.347-347, Article 347
• Main Authors: Su, Xiaosan, Fan, Yaodong, Yang, Liu, Huang, Jie, Qiao, Fei, Fang, Yu, Wang, Jun
• Format: Article
• Language: English
• Subjects: Adrenergic receptors; Aged; Anesthesia; Angiogenesis; Animals; Cancer metastasis; Cancer surgery; Care and treatment; CD11b antigen; CD14 antigen; Cell Line, Tumor; Cell Proliferation - drug effects; Complications and side effects; Dendritic cells; Dexmedetomidine; Dexmedetomidine - adverse effects; Dosage and administration; Expansion; Female; Histocompatibility antigen HLA; Humans; Immunosuppressive agents; Immunosuppressive Agents - adverse effects; Lung cancer; Lung Neoplasms - pathology; Lung Neoplasms - surgery; Male; Management; Metastases; Metastasis; Mice; Mice, Inbred C57BL; Middle Aged; Monocytes; Monocytes - drug effects; Monocytes - pathology; Myeloid-derived suppressor cells; Myeloid-Derived Suppressor Cells - drug effects; Myeloid-Derived Suppressor Cells - pathology; Neoplasm Metastasis; Neovascularization, Pathologic - pathology; Neutrophils; Patients; Perioperative care; Postoperative period; Receptors, Adrenergic, alpha-2 - metabolism; Risk factors; Suppressor cells; Surgery; Tumors; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - biosynthesis
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-018-1727-9

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. 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. 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 α -adrenergic receptor. Using an experimental tumour metastasis mouse model, we demonstrated that the numbers of metastases on lung surface and CD11b Ly6C Ly6G 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. 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.