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CXCR4 antagonist inhibits perineural invasion of adenoid cystic carcinoma
  1. Woo-Jin Jeong1,
  2. Ik Joon Choi2,
  3. Min-Woo Park3,
  4. Soo-Youn An4,
  5. Eun-Hui Jeon1,
  6. Jin Ho Paik5,
  7. Myung-Whun Sung6,7,
  8. Soon-Hyun Ahn1
  1. 1Department of Otorhinolaryngology—Head & Neck Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
  2. 2Department of Otolaryngology—Head & Neck Surgery, Korea Cancer Center Hospital, Seoul, South Korea
  3. 3Department of Otorhinolaryngology—Head & Neck Surgery, Korea University Anam Hospital, Seoul, South Korea
  4. 4Department of Otolaryngology—Head & Neck Surgery, Dongnam Institute of Radiological & Medical Sciences, Busan, South Korea
  5. 5Department of Pathology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
  6. 6Department of Otorhinolaryngology—Head & Neck Surgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, South Korea
  7. 7Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea
  1. Correspondence to Professor Soon-Hyun Ahn, Department of Otorhinolaryngology—Head & Neck Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 300 Gumi-dong, Bundang-gu, Seongnam 463-707, South Korea; ahnsh30{at}snu.ac.kr

Abstract

Aim 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.

  • HEAD AND NECK CANCER
  • SALIVARY GLAND TUMOURS
  • SURGERY

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