title: Formylpeptide receptor 1 mediates the tumorigenicity of human hepatocellular carcinoma cells.
abstract: G protein-coupled chemoattractant receptors (GPCRs) have been implicated in cancer progression. Formylpeptide receptor 1 (FPR1) was originally identified as a GPCR mediating anti-microbial host defense. However, the role of FPR1 in tumorigenesis remains poorly understood. The current study aims to investigate the potential of FPR1 to regulate human hepatoma growth and invasion. We found the FPR1 gene and protein expression in human intratumoral and peritumoral tissues of hepatocellular carcinoma (HCC) specimens and in human hepatoma cell lines. FPR1 activation mediated the migration, calcium mobilization and ERK-dependent IL-8 production by hepatic cancer cells. FPR1 knockdown substantially reduced the tumorigenicity of hepatoma cells in nude mice. Necrotic hepatic tumor cells released factor(s) that activated FPR1 in live tumor cells. Our results indicate a critical role of FPR1 in the progression of malignant human hepatic cancer. FPR1 thus may represent a molecular target for the development of novel anti-hepatoma therapeutics.
authors.affiliation: Department of Image Guided Therapy, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine , Guangzhou, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital, Sun Yat-sen University , Guangzhou, China.
authors.forename: Huanyu
authors.initials: H
authors.lastname: Wang
authors.affiliation: Shanghai Tenth People's Hospital, Tongji University School of Medicine , Shanghai, China.
authors.forename: Tianshu
authors.initials: T
authors.lastname: Yang
authors.affiliation: School of Materials and Engineering, South China University of Technology , Guangzhou, China.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Su
authors.affiliation: Shanghai Tenth People's Hospital, Tongji University School of Medicine , Shanghai, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Fang
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital, Sun Yat-sen University , Guangzhou, China.
authors.forename: Yafeng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Shanghai Tenth People's Hospital, Tongji University School of Medicine , Shanghai, China.
authors.forename: Jiazhu
authors.initials: J
authors.lastname: Fang
authors.affiliation: Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai, China.
authors.forename: Xinwei
authors.initials: X
authors.lastname: Hou
authors.affiliation: Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Le
authors.affiliation: Laboratory of Molecular Immunoregulation, National Cancer Institute , Frederick, MD, USA.
authors.forename: Keqiang
authors.initials: K
authors.lastname: Chen
authors.affiliation: Laboratory of Molecular Immunoregulation, National Cancer Institute , Frederick, MD, USA.
authors.forename: Ji Ming
authors.initials: JM
authors.lastname: Wang
authors.affiliation: Shanghai Tenth People's Hospital, Tongji University School of Medicine , Shanghai, China.
authors.forename: Shao Bo
authors.initials: SB
authors.lastname: Su
authors.affiliation: Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Lin
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital, Sun Yat-sen University , Guangzhou, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
keywords: Cancer; GPCR; HepG2; IL-8; liver