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Inflammation

, Volume 37, Issue 3, pp 984–992 | Cite as

Formyl Peptide Receptor Suppresses Melanoma Development and Promotes NK Cell Migration

  • Jian Liu
  • Jun Li
  • Xiang Zeng
  • Zhiguo Rao
  • Jianfei Gao
  • Bicheng Zhang
  • Yong Zhao
  • Bo Yang
  • Zhigang Wang
  • Lifang Yu
  • Weixing Wang
Article

Abstract

In order to understand how tumor cells can escape immune surveillance mechanisms and thus develop antitumor therapies, it is critically important to investigate the mechanisms by which the immune system interacts with the tumor microenvironment. In our current study, wild-type mice were inoculated with melanoma cell line B16-F10 (1 × 106/mouse) and treated with the formyl peptide receptor (FPR) agonist WKYMVm or the FPR antagonist WRW4. Growth of melanoma cell line B16-F10 was significantly inhibited in WKYMVm-treated mice and markedly promoted in WRW4-treated mice compared with control. Decreased number of myeloid-derived suppressor cells (MDSCs) and increased NK cell infiltration in tumor tissues were detected from WKYMVm-treated mice. Next, we showed that depletion of NK cell significantly increased tumor development in B16 tumor-bearing mice compared with the control group, and the suppressed tumor-developing effect of WKYMVm in B16 melanoma was abrogated with NK cell depletion. We also found that WKYMVm stimulates chemotactic migration in NK cells via the FPR family, and this was dependent on extracellular signal-related kinase (ERK) activation. Moreover, in our further experiment, we showed that the increased infiltration of NK cell and promoted NK cell chemotaxis in B16 melanoma induced by WKYMVm were both abolished with ERK inhibitor PD98059 administration. In conclusion, the FPR family promoted NK cell migration through ERK activation and inhibited B16 melanoma growth in a murine model.

KEY WORDS

FPR NK cell ERK melanoma 

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Jian Liu
    • 1
  • Jun Li
    • 2
  • Xiang Zeng
    • 3
  • Zhiguo Rao
    • 1
  • Jianfei Gao
    • 1
  • Bicheng Zhang
    • 1
  • Yong Zhao
    • 1
  • Bo Yang
    • 1
  • Zhigang Wang
    • 1
  • Lifang Yu
    • 1
  • Weixing Wang
    • 1
  1. 1.Department of Oncology, Wuhan General Hospital of Guangzhou CommandPeople’s Liberation ArmyWuhanChina
  2. 2.Department of Oncology, The Central Hospital of Wuhan, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
  3. 3.Department of OncologyGeneral Hospital of The Yangtze River ShippingWuhanChina

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