PMID- 25402728 OWN - NLM STAT- MEDLINE DCOM- 20150814 LR - 20190221 IS - 1949-2553 (Electronic) IS - 1949-2553 (Linking) VI - 6 IP - 1 DP - 2015 Jan 1 TI - Dendritic cells respond to nasopharygeal carcinoma cells through annexin A2-recognizing DC-SIGN. PG - 159-70 AB - Dendritic cells (DCs) play an essential role in immunity and are used in cancer immunotherapy. However, these cells can be tuned by tumors with immunosuppressive responses. DC-specific intercellular adhesion molecule 3-Grabbing Nonintegrin (DC-SIGN), a C-type lectin expressed on DCs, recognizes certain carbohydrate structures which can be found on cancer cells. Nasopharyngeal carcinoma (NPC) is an epithelial cell-derived malignant tumor, in which immune response remains unclear. This research is to reveal the molecular link on NPC cells that induces the immunosuppressive responses in DCs. In this article, we report identification of annexin A2 (ANXA2) on NPC cells as a ligand for DC-SIGN on DCs. N-linked mannose-rich glycan on ANXA2 may mediate the interaction. ANXA2 was abundantly expressed in NPC, and knockdown of ANXA2 suppressed NPC xenograft in mice, suggesting a crucial role of ANXA2 in NPC growth. Interaction with NPC cells caused DC-SIGN activation in DCs. Consequently DC maturation and the proinflammatory interleukin (IL)-12 production were inhibited, and the immunosuppressive IL-10 production was promoted. Blockage of either DC-SIGN or ANXA2 eliminated the production of IL-10 from DCs. This report suggests that suppression of ANXA2 at its expression or glycosylation on NPC may improve DC-mediated immunotherapy for the tumor. FAU - Chao, Pin-Zhir AU - Chao PZ AD - Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Department of Otolaryngology, Shuang-Ho Hospital, New Taipei, Taiwan. FAU - Hsieh, Ming-Shium AU - Hsieh MS AD - Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Department of Orthopedics, En Chu Kong Hospital, New Taipei, Taiwan. FAU - Cheng, Chao-Wen AU - Cheng CW AD - Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. FAU - Hsu, Tin-Jui AU - Hsu TJ AD - School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan. FAU - Lin, Yun-Tien AU - Lin YT AD - School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan. FAU - Lai, Chang-Hao AU - Lai CH AD - School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan. FAU - Liao, Chen-Chung AU - Liao CC AD - Proteomics Research Center, National Yang-Ming University, Taipei, Taiwan. FAU - Chen, Wei-Yu AU - Chen WY AD - Department of Pathology, Wan Fang Hospital, Taipei, Taiwan. FAU - Leung, Ting-Kai AU - Leung TK AD - Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. FAU - Lee, Fei-Peng AU - Lee FP AD - Department of Otolaryngology, Head and Neck Surgery, Wan-Fang Medical Center, Taipei, Taiwan. FAU - Lin, Yung-Feng AU - Lin YF AD - School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan. FAU - Chen, Chien-Ho AU - Chen CH AD - School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Oncotarget JT - Oncotarget JID - 101532965 RN - 0 (ANXA2 protein, human) RN - 0 (Annexin A2) RN - 0 (Cell Adhesion Molecules) RN - 0 (Cytokines) RN - 0 (DC-specific ICAM-3 grabbing nonintegrin) RN - 0 (Immunoglobulin G) RN - 0 (Immunosuppressive Agents) RN - 0 (Lectins, C-Type) RN - 0 (Ligands) RN - 0 (Polysaccharides) RN - 0 (Receptors, Cell Surface) RN - 130068-27-8 (Interleukin-10) RN - 187348-17-0 (Interleukin-12) SB - IM MH - Animals MH - Annexin A2/*metabolism MH - Carcinoma MH - Cell Adhesion Molecules/*metabolism MH - Cell Line, Tumor MH - Cytokines/metabolism MH - Dendritic Cells/*cytology MH - *Gene Expression Regulation, Neoplastic MH - Glycosylation MH - Humans MH - Immunoglobulin G/chemistry MH - Immunoprecipitation MH - Immunosuppressive Agents/chemistry MH - Immunotherapy/methods MH - Interleukin-10/metabolism MH - Interleukin-12/metabolism MH - Lectins, C-Type/*metabolism MH - Ligands MH - Mice MH - Mice, Inbred NOD MH - Mice, SCID MH - Nasopharyngeal Carcinoma MH - Nasopharyngeal Neoplasms/*metabolism MH - Neoplasm Transplantation MH - Polysaccharides/chemistry MH - RNA Interference MH - Receptors, Cell Surface/*metabolism PMC - PMC4381585 COIS- Conflict of Interest Disclosures All the authors declare no conflict of interest on the publication. EDAT- 2014/11/18 06:00 MHDA- 2015/08/15 06:00 PMCR- 2015/01/01 CRDT- 2014/11/18 06:00 PHST- 2014/09/03 00:00 [received] PHST- 2014/11/06 00:00 [accepted] PHST- 2014/11/18 06:00 [entrez] PHST- 2014/11/18 06:00 [pubmed] PHST- 2015/08/15 06:00 [medline] PHST- 2015/01/01 00:00 [pmc-release] AID - 2700 [pii] AID - 10.18632/oncotarget.2700 [doi] PST - ppublish SO - Oncotarget. 2015 Jan 1;6(1):159-70. doi: 10.18632/oncotarget.2700.