Involvement of IL-10 and TGF-β in HLA-E-mediated neuroblastoma migration and invasion
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Zijun Zhen1,2,3, Xiaofang Guo1,2,3, Ru Liao1,2,3, Kaibin Yang1,4, Litong Ye1,4, Zhiyao You1,4
1Department of Pediatric Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China
2State Key Laboratory of Oncology in South China, Guangzhou, 510060, China
3Collaborative Innovation Center of Cancer Medicine, Guangzhou, 510060, China
4Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, China
Zijun Zhen, email: firstname.lastname@example.org
Keywords: neuroblastoma, migration, invasion, HLA-E, IL-10
Received: March 11, 2016 Accepted: June 03, 2016 Published: June 14, 2016
Human leukocyte antigen (HLA)-E is highly expressed in a variety of tumors and, in addition to immune escape, may promote tumor growth via other mechanisms. However, the role of HLA-E in neuroblastoma (NB) migration and invasion is unknown. In the present study, HLA-E expression in human NB tumors was measured by immunohistochemistry. The effect of HLA-E on NB cell migration and invasion was studied in vitro and in vivo, as well as the effect of HLA-E on natural killer (NK)-cell cytotoxicity. HLA-E was expressed in 70.2% of the NB tumor tissues examined. HLA-E expression by NB cells inhibited NK-cell cytotoxicity and induced the release of interleukin (IL)-10 and transforming growth factor (TGF)-β1. HLA-E and the released cytokines enhanced the ability of NB cells migration and invasion. NK cell infusion did not inhibit the growth of NB cells with high HLA-E expression but instead increased the number of metastatic cells in the bone marrow. Taken together, the results indicate that IL-10 and TGF-β are involved in HLA-E-mediated NB migration and invasion. Thus, HLA-E may be a new treatment target in NB.
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