Division of Hepatology and Gene Therapy, Proteomics Unit. Center for Applied Medical Research (CIMA), University of Navarra, 31008 Pamplona, Spain.
J Proteomics. 2009 Nov 2;73(1):153-60. doi: 10.1016/j.jprot.2009.06.008. Epub 2009 Jun 21.
Recent studies based on animal models have shown the advantages and potential of oncolytic viral therapy using HSV-1 -based replication-competent vectors in the treatment of liver tumors, but little is known about the cellular targets that are modulated during viral infection. In the present work, we have studied the effects of intratumoral injections of HSV-1 Cgal(+) strain in a murine model of human hepatoma xenografts. Viral replication was assessed for more than 1month, leading to a significant reduction of tumor growth rate mediated, in part, by a cyclin B dependent cell proliferation arrest. Early events resulting in this effect were analyzed using a proteomic approach. Protein extracts from xenografted human hepatomas treated with saline or HSV-1 Cgal(+) strain during 24h were compared by 2-D DIGE and differential spots were identified by nanoLC-ESI-MS/MS. Alterations on glutathione S transferase 1 Omega, and ERp29 suggest novel HSV-1 Cgal(+) targets in solid liver tumors. Additionally, ERp29 showed a complex differential isoform pattern upon HSV-1 Cgal(+) infection, suggesting regulatory mechanisms based on post-translational modification events.
最近的动物模型研究表明，使用基于单纯疱疹病毒 1 的复制型载体进行溶瘤病毒治疗在治疗肝肿瘤方面具有优势和潜力，但对于病毒感染过程中调节的细胞靶标知之甚少。在本工作中，我们研究了 HSV-1 Cgal(+)株在人肝癌异种移植鼠模型中的肿瘤内注射的效果。病毒复制评估超过 1 个月，导致肿瘤生长速率显著降低，部分原因是 cyclin B 依赖性细胞增殖停滞。使用蛋白质组学方法分析导致这种效应的早期事件。通过 2-D DIGE 比较用生理盐水或 HSV-1 Cgal(+)株处理的异种移植人肝癌的蛋白质提取物，并通过纳升 LC-ESI-MS/MS 鉴定差异点。谷胱甘肽 S 转移酶 1 Omega 和 ERp29 的改变表明，在实体肝肿瘤中存在新型 HSV-1 Cgal(+)靶标。此外，HSV-1 Cgal(+)感染后 ERp29 显示出复杂的差异同工型模式，表明基于翻译后修饰事件的调节机制。
