title: CXCR4 antagonist inhibits perineural invasion of adenoid cystic carcinoma.
abstract: OBJECTIVE
  Perineural invasion and expression of CXCR4 is characteristic of adenoid cystic carcinoma (ACC). Herein, we aimed to demonstrate CXCR4 expression in ACC, identify its association with perineural invasion and investigate the impact of CXCR4 inhibitor in vitro and in a murine perineural invasion model.
  
  
  METHODS
  Expression of CXCR4 was assessed in ACC cell lines and in human tissue. The effects of gene knockdown using siRNA and specific blocker of CXCR4 (AMD3100) were evaluated in vitro. A preclinical perineural invasion model was developed using BALB/c nude mouse. The effect of AMD3100 was evaluated in vivo.
  
  
  RESULTS
  CXCR4 was highly expressed in aggressive strains of ACC in vitro, in the tumour in the animal model and in the tumour of human tissue. SDF-1 expression was also demonstrated in the nerve of murine and human tissue. Gene knockdown by siRNA and inhibition by a CXCR4-specific inhibitor AMD3100 effectively abrogated invasion but not proliferation of ACC in vitro. The rate of perineural invasion was significantly decreased with AMD3100 treatment in the animal model.
  
  
  CONCLUSIONS
  CXCR4 is associated with perineural invasion in ACC. AMD3100, which can effectively diminish perineural invasion of ACC, may have an adjuvant role in the management of ACC.
authors.affiliation: Department of Otorhinolaryngology-Head & Neck Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.
authors.forename: Woo-Jin
authors.identifier: http://orcid.org/0000-0001-8577-6964
authors.initials: WJ
authors.lastname: Jeong
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, Korea Cancer Center Hospital, Seoul, South Korea.
authors.forename: Ik Joon
authors.initials: IJ
authors.lastname: Choi
authors.affiliation: Department of Otorhinolaryngology-Head & Neck Surgery, Korea University Anam Hospital, Seoul, South Korea.
authors.forename: Min-Woo
authors.initials: MW
authors.lastname: Park
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, Dongnam Institute of Radiological & Medical Sciences, Busan, South Korea.
authors.forename: Soo-Youn
authors.initials: SY
authors.lastname: An
authors.affiliation: Department of Otorhinolaryngology-Head & Neck Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.
authors.forename: Eun-Hui
authors.initials: EH
authors.lastname: Jeon
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.
authors.forename: Jin Ho
authors.initials: JH
authors.lastname: Paik
authors.affiliation: Department of Otorhinolaryngology-Head & Neck Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, South Korea Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Myung-Whun
authors.initials: MW
authors.lastname: Sung
authors.affiliation: Department of Otorhinolaryngology-Head & Neck Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.
authors.forename: Soon-Hyun
authors.initials: SH
authors.lastname: Ahn
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001596:Benzylamines; D003528:Carcinoma, Adenoid Cystic / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D000080027:Cyclams; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D017933:Peripheral Nervous System / Q000473:pathology*; D034622:RNA Interference; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012468:Salivary Gland Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D001596:Benzylamines; C527276:CXCR4 protein, human; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; C088327:plerixafor
keywords: HEAD AND NECK CANCER; SALIVARY GLAND TUMOURS; SURGERY