Biomedical Journal

Biomedical Journal

Volume 39, Issue 4, August 2016, Pages 261-271
Biomedical Journal

Original Article
Spontaneous metastases in immunocompetent mice harboring a primary tumor driven by oncogene latent membrane protein 1 from Epstein–Barr virus

https://doi.org/10.1016/j.bj.2015.12.003Get rights and content
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open access

Abstract

Background

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).

Methods

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.

Results

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.

Conclusions

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.

Keywords

Nasopharyngeal carcinoma (NPC)
Epstein–Barr virus (EBV)
Oncogene latent membrane protein 1 (N-LMP1)
Tumor mouse model
Distant metastasis

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Peer review under responsibility of Chang Gung University.

1

Pu-Yuan Chang and Yenlin Huang contributed equally to this study.