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Clinical & Experimental Metastasis

, Volume 30, Issue 2, pp 133–142 | Cite as

Expression and function of CXCR4 in human salivary gland cancers

  • Daisuke Uchida
  • Nobuyuki Kuribayashi
  • Makoto Kinouchi
  • Go Ohe
  • Tetsuya Tamatani
  • Hirokazu Nagai
  • Youji Miyamoto
Research Paper

Abstract

Salivary gland cancers (SGCs) frequently metastasize to cervical lymph nodes and distant organs. Currently, the mechanisms responsible for the metastatic behavior of SGC cells are not fully understood. We previously demonstrated that the stromal cell-derived factor-1 (SDF-1; also known as CXCL12)/CXCR4 system is involved in the establishment of metastasis in oral squamous cell carcinoma. In the present study, we investigated the role of CXCR4 in the metastatic behavior of SGCs. We examined the expression of CXCR4 mRNA and protein in human SGC cell lines by quantitative RT-PCR and western blotting, respectively. The expression of CXCR4 mRNA and protein were frequently upregulated in 5 out of 6 SGC cell lines. Functional CXCR4 expression was demonstrated by the ability of these SGC cell lines to migrate toward an SDF-1 gradient. SDF-1 rapidly activated extracellular signal-regulated kinase (ERK)1/2 in SGC cell lines. Immunohistochemical analysis revealed that CXCR4 protein expression was detected in either the nucleus or cytoplasm of cancer cells in 16 out of 20 tissues of adenoid cystic carcinoma (ACC) and in 4 out of 6 tissues of mucoepidermoid carcinoma, which are representative of SGC. Furthermore, ACC cell lines exhibited dramatic metastasis to the lung following intravenous inoculation, whereas AMD3100, a CXCR4 antagonist, significantly inhibited lung metastasis of the cells, ameliorated body weight loss and improved the survival rate of tumor-bearing nude mice. These results indicate that CXCR4 expression contributes to the metastatic potential of SGCs.

Keywords

Salivary gland cancers CXCR4 Metastases Adenoid cystic carcinoma Mucoepidermoid carcinoma 

Abbreviations

SGCs

Salivary gland cancers

ACC

Adenoid cystic carcinoma

MEC

Mucoepidermoid carcinoma

Notes

Acknowledgments

We thank Dr. Naozumi Ishimaru (Department of Oral Molecular Pathology, Tokushima University School of Dentistry) for valuable advice on histopathology. We also thank Drs. Tomitaro Onoue and Begum Nasima-Mila for technical assistance. This study was supported in part by a Grant-in-Aid for Scientific Research (C) (23592964).

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Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Daisuke Uchida
    • 1
  • Nobuyuki Kuribayashi
    • 1
  • Makoto Kinouchi
    • 1
  • Go Ohe
    • 1
  • Tetsuya Tamatani
    • 1
  • Hirokazu Nagai
    • 1
  • Youji Miyamoto
    • 1
  1. 1.Subdivision of Molecular Oral Medicine, Division of Integrated Sciences of Translational Research, Department of Oral Surgery, Institute of Health BiosciencesThe University of Tokushima Graduate SchoolTokushimaJapan

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