title: Spontaneous metastases in immunocompetent mice harboring a primary tumor driven by oncogene latent membrane protein 1 from Epstein-Barr virus.
abstract: In vitro and clinical studies suggest that the oncogene LMP1 (latent membrane protein 1) encoded by Epstein-Barr virus (EBV) plays a role in the development of nasopharyngeal carcinoma (NPC) and the formation of metastases in immunocompetent individuals. However, whether LMP1 itself is sufficient to drive these events in immunocompetent hosts remains elusive due to the lack of appropriate experimental models. The aim of this study was to study LMP1-dependent tumorigenesis and metastasis in BALB/c mice inoculated with BALB/c-3T3 cells expressing N-LMP1 (a Taiwanese NPC variant).
  
  
  
  Following cancer cell inoculation, metastasis formation was monitored over time using PCR analysis of LMP1 as tumor marker. We also used a luciferase (Luc)-containing N-LMP1 and bioluminescent imaging (BLI) to monitor metastasis formation in a non-invasive manner.
  
  
  
  N-LMP1 appeared early in draining lymph nodes and in various distant organs before the rapid growth of the primary tumor. Lung metastasis was observed by BLI and further confirmed by histological examination. Furthermore, we detected luciferase signals in the lungs, even before the animals were sacrificed.
  
  
  
  Our results demonstrate the high metastatic character of N-LMP1 in immunocompetent hosts. Systemic tumor dissemination occurs even before aggressive tumor growth at the primary site, suggesting that early treatment of primary LMP1-associated tumors and distant micro-metastases is critical to achieve positive results.
authors: Tumor Biology Laboratory, Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors: Pu-Yuan
authors: PY
authors: Chang
authors: Department of Anatomic Pathology, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors: Yenlin
authors: Y
authors: Huang
authors: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors: Tzu-Yuan
authors: TY
authors: Hung
authors: Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors: Kowit-Yu
authors: KY
authors: Chong
authors: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Molecular Medical Research Center, Chang Gung University, Taoyuan, Taiwan.
authors: Yu-Sun
authors: YS
authors: Chang
authors: Tumor Biology Laboratory, Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan. Electronic address: cckchao@mail.cgu.edu.tw.
authors: Chuck C-K
authors: CC
authors: Chao
authors: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan. Electronic address: kpc@mail.cgu.edu.tw.
authors: Kai-Ping N
authors: KN
authors: Chow
mesh_terms: D000818:Animals; D004854:Herpesvirus 4, Human; D007121:Immunocompetence; D008175:Lung Neoplasms / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D009303:Nasopharyngeal Neoplasms / Q000473:pathology*; D009362:Neoplasm Metastasis / Q000473:pathology*; D009374:Neoplasms, Experimental / Q000473:pathology; D014763:Viral Matrix Proteins / Q000502:physiology*
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins
keywords: Distant metastasis; Epstein–Barr virus (EBV); Nasopharyngeal carcinoma (NPC); Oncogene latent membrane protein 1 (N-LMP1); Tumor mouse model