Epstein-Barr virus latent nuclear antigens can induce metastasis in a nude mouse model.
Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus associated with the development of both lymphoid and epithelial tumors. The EBV critical latent antigens EBNA1 and EBNA3C interact with Nm23-H1, a known suppressor of cell migration and tumor metastasis. This interaction is critical for the regulation of downstream cellular genes involved in tumorigenesis and cell migration. The significance of these interactions was determined in nude mice using cancer cells expressing both EBV antigens and Nm23-H1. The EBV antigens promoted the growth of transformed cells in vivo, but their expression was less critical during the later stage of tumor development. The expression of Nm23-H1 affected the growth of cancer cells and suppressed their metastatic potential. This effect was effectively rescued by the expression of both EBV antigens. Interestingly, the prometastatic potential of EBNA3C was greater than that of EBNA1, which triggered a dramatic immune response, as indicated by increased spleen size and development of ascites in the mice. These studies now bridge the expression of the EBV antigens with tumorigenesis and metastasis and widen the range of potential targets for development of therapies for EBV-associated malignancies.
Kaul
Rajeev
R
Department of Microbiology and Tumor Virology Program of the Abramson Comprehensive Cancer Center, University of Pennsylvania School of Medicine, 201E Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104, USA.
Murakami
Masanao
M
Choudhuri
Tathagata
T
Robertson
Erle S
ES
D000818:Animals; D000956:Antigens, Viral / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D023421:Models, Animal; D054778:NM23 Nucleoside Diphosphate Kinases; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D009701:Nucleoside-Diphosphate Kinase / Q000378:metabolism*
D000956:Antigens, Viral; C498774:EBNA-3C, epstein-barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; D054778:NM23 Nucleoside Diphosphate Kinases; C517938:NME1 protein, human; C517939:Nme1 protein, mouse; D009701:Nucleoside-Diphosphate Kinase; C417029:EBV-encoded nuclear antigen 1