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Research Articles: Therapeutics, Targets, and Development

Formyl peptide receptor-like 1–mediated endogenous TRAIL gene expression with tumoricidal activity

National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

Requests for reprints: Dexian Zheng or Yanxin Liu, Institute of Basic Medical Sciences, CAMS, 5 Dong Dan San Tiao, Beijing 100005, China. Phone: 86-10-6529-6409; Fax: 86-10-6510-5102. E-mail: zhengdx{at}pumc.edu.cn

Abstract

Formyl peptide receptor-like 1 (FPRL1), which is a G protein–coupled receptor of chemoattractant subfamily, plays an important role in the regulation of host defense against pathogenic infection and the chemotactic and activating effects of Aß₄₂ on mononuclear phagocytes as well as in the elimination of damaged or pathogen-infected cells. In the present study, we showed that stimulation of FPRL1 agonist ligands (W peptide from a synthetic peptide library, N36 peptide from HIV-1 gp41, and F peptide from HIV-1 envelope protein gp120) elevated endogenous tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) expression in human THP-1 monocytes, primary neutrophils, and mouse leukocytes. Activation of nuclear factor B was required by the FPRL1-mediated TRAIL expression in the human THP-1 cells and primary neutrophils. The increased TRAIL expression in the mice significantly suppressed the growth of transplanted mouse liver tumor cells by inducing apoptotic cell death. Together, these data provide novel evidence for the physiologic role of FPRL1 and TRAIL in tumor immune surveillance and innate immunity, and implicate a novel strategy for cancer therapy by triggering the endogenous TRAIL expression via stimulation of G protein–coupled receptor FPRL1. [Mol Cancer Ther 2007;6(10):2618–25]

Grant support: National Natural Science Foundation of China grant 30571687 and State Key Basic Research Program of China grant 2007CB507404.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 4/23/07; revised 6/28/07; accepted 8/31/07.