Carcinogenesis Advance Access published online on May 29, 2009
Carcinogenesis, doi:10.1093/carcin/bgp135
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Decoy receptor 3, upregulated by Epstein-Barr virus latent membrane protein 1, enhances nasopharyngeal carcinoma cell migration and invasion
1 Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan
2 Department of Pathology, Taipei Medical University, Taipei
3 Taipei Municipal Wangfang Hospital, Taipei, Taiwan
4 Department of Pathology, Taipei Veterans General Hospital, Taipei, Taiwan
Corresponding author. Mailing address: Room 408, Institute of Microbiology and Immunology, National Yang-Ming University, No. 155, Section 2, Linong Street, Taipei 112, Taiwan. Phone: 886-2-2826-7180. Fax: 886-2-2821-2880. E-mail: cjchen{at}ym.edu.tw
Decoy receptor 3 (DcR3), a member of tumor necrosis factor receptor superfamily, has been implicated in tumorigenesis through its abilities to modulate immune responses and induce angiogenesis. Epstein-Barr virus (EBV), a ubiquitous 
-herpesvirus, is associated with malignancies including nasopharyngeal carcinoma (NPC). Previous studies show that DcR3 is overexpressed in EBV-positive lymphomas and Rta, an EBV transcription activator, can upregulate DcR3 in Burkitt lymphoma cell lines. However, DcR3 expression has not been demonstrated in EBV-associated NPC nor have there been any EBV latent genes linked to DcR3 upregulation. Here we showed DcR3 was overexpressed in NPC. Higher DcR3 expression score and DcR3-positive rate were found in metastatic NPC than in primary NPC tissues, suggesting DcR3 may enhance cell metastatic potential. This hypothesis is supported by our observation that NPC HONE-1 cells overexpressing DcR3 exhibited significant higher migration and invasion abilities in vitro. We found besides Rta, EBV latent protein 1 (LMP1) can upregulate DcR3 via NF-
B and PI3K signaling events. Approximate 75% of LMP1-positive NPC tissues overexpressed DcR3, suggesting LMP1 may enhance DcR3 expression in vivo. Data herein suggested that increasing DcR3 expression by LMP1 not only helps EBV-associated cancer cells gain survival advantage by preventing host immune detection, but also increases the chance of cancer metastasis by enhancing cell migration and invasion. All these DcR3-mediated events facilitate normal cells to gain cancer hallmarks.
Key Words: DcR3 • LMP1 • NPC • cell migration and invasion
Received January 15, 2009; revised May 20, 2009; accepted May 23, 2009.