Dendritic cells recognize glycosylated Annexin A2 on nasopharyngeal carcinoma cells through DC-SIGN

• Main Authors: Tin-Jui Hsu, 許庭睿
• Other Authors: Chien-Ho Chen
• Format: Others
• Language: en_US
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/99671824772185369328

碩士 === 臺北醫學大學 === 醫學檢驗暨生物技術學系 === 101 === NPC is an epithelial cell-derived malignant tumor that mainly occurs in Southeast Asia including Taiwan. Radiotherapy and chemotherapy are the primary treatments of nasopharyngeal cancer, but normal tissues are usually affected with various side effects. There is an unmet medical need to develop a therapeutic method to distinguish cancer cells from normal cells. Dendritic cells (DCs) play an essential role in immunity against tumor and can be used as an important tool to conduct cancer immunotherapy. However, DCs also express a C-type lectin, DC-pecific ICAM-3-Grabbing Nonintegrin (DC-SIGN), that can induce suppressive immune responses by recognizing carbohydrate structure. Many studies indicated that cancer cells escape from immunosurveillance by modulating the functions of DCs via DC-SIGN. In this study, we found that DC-SIGN ligands were expressed on NPC cells. When treated with NPC cells or cell components, DCs produced immunosuppressive cytokine IL-10 and immature. Then we performed co-immunoprecipitation and identified annexin A2 on NPC cells as a candidate ligand for DC-SIGN . When annexin A2 was knocked down or blocked in NPC cells, DC-SIGN-binding capacity on NPC cells and IL-10 production in DCs were reduced, suggesting a specific immunosuppressive response of DCs by NPC through DC-SIGN-annexin A2 interactions. Finally we demonstrated that N-glycans on annexin A2 and other mannose-containing DC-SIGN ligands on NPC cells were important for DC-SIGN activity. Annexin A2 is a potential targeting for anti- NPC therapy.