Epstein-Barr virus latent nuclear antigens can induce metastasis in a nude mouse model
Epstein-Barr virus latent nuclear antigens can induce metastasis in a nude mouse model
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DOI：
10.1128/jvi.00886-07
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发表时间：
2007-10-01
影响因子：
5.4
通讯作者：
Robertson, Erle S.
中科院分区：
文献类型：
--
作者：
Kaul, Rajeev;Murakami, Masanao;Robertson, Erle S.
eb病毒（EBV）是一种普遍存在的人类疱疹病毒，与淋巴和上皮肿瘤的发生有关。EBV关键潜伏抗原EBNA1和EBNA3C与Nm23-H1相互作用，Nm23-H1是已知的细胞迁移和肿瘤转移的抑制因子。这种相互作用对参与肿瘤发生和细胞迁移的下游细胞基因的调节至关重要。利用同时表达EBV抗原和Nm23-1H的癌细胞，在裸鼠中确定了这些相互作用的意义。EBV抗原在体内促进转化细胞的生长，但在肿瘤发展的后期，它们的表达不那么重要。Nm23-1H的表达影响癌细胞的生长，抑制癌细胞的转移潜能。两种EBV抗原的表达有效地挽救了这种效应。有趣的是，EBNA3C的原转移潜力比EBNA1大，这引发了戏剧性的免疫反应，正如小鼠脾脏大小增加和腹水的发展所表明的那样。这些研究现在将EBV抗原的表达与肿瘤发生和转移联系起来，并扩大了EBV相关恶性肿瘤治疗开发的潜在靶点范围。
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 Nm23-1H. 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 Nm23-1H 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.