Xing Yan, Wang Yisong, Wang Shijie, Wang Xin, Fan Dongying, Zhou Dabiao, An Jing
Department of Microbiology and Parasitology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Transl Res. 2016 Nov;177:113-126. doi: 10.1016/j.trsl.2016.06.008. Epub 2016 Jul 13.
The etiology of malignant glioma remains unclear. To examine the association between glioma and human cytomegalovirus (HCMV) infection and the possible mechanism through which HCMV contributes to malignant glioma, we investigated the expression of HCMV components and an angiogenesis marker, endocan, in 79 glioma specimens and 8 control brain samples. HCMV pp65 protein and DNA were detected in 65.8% (52 of 79) and 54.4% (43 of 79) of glioma specimens, respectively. The positive rate and expression levels of pp65 were significantly correlated with the glioma grades. The endocan expression was detected in 78.5% (62 of 79) of glioma specimens, and elevated endocan immunoreactivity was also significantly associated with high-grade glioma. The pp65 was predominantly detected and colocalized with endocan in the cytoplasm of tumor cells. Importantly, there was a significant positive correlation in detection rates between those 2 proteins. In control samples, neither HCMV pp65 nor endocan expression was detected. Moreover, the serum endocan levels in glioma patients were markedly higher than that in healthy subjects. In in vitro study, HCMV infection induced the expression of interleukin 6 and tumor necrosis factor-α in human glioblastoma U87 MG (U87) cells and human umbilical vein endothelial cells (HUVECs). Furthermore, elevated endocan levels were also observed in HCMV-infected U87 cells and HUVECs and antiviral treatment with ganciclovir reduced the endocan expression. These results suggest HCMV infection leads to glioma progression through an upregulation of endocan and the secretion of inflammatory cytokines. Thus, anti-HCMV treatment may represent a potentially novel therapeutic strategy for glioma.
恶性胶质瘤的病因仍不清楚。为了研究胶质瘤与人类巨细胞病毒（HCMV）感染之间的关联以及HCMV促成恶性胶质瘤的可能机制，我们调查了79例胶质瘤标本和8例对照脑样本中HCMV成分及一种血管生成标志物内皮糖蛋白的表达情况。分别在65.8%（79例中的52例）和54.4%（79例中的43例）的胶质瘤标本中检测到HCMV pp65蛋白和DNA。pp65的阳性率和表达水平与胶质瘤分级显著相关。在78.5%（79例中的62例）的胶质瘤标本中检测到内皮糖蛋白表达，内皮糖蛋白免疫反应性升高也与高级别胶质瘤显著相关。pp65主要在肿瘤细胞的细胞质中被检测到并与内皮糖蛋白共定位。重要的是，这两种蛋白的检测率之间存在显著正相关。在对照样本中，未检测到HCMV pp65和内皮糖蛋白表达。此外，胶质瘤患者的血清内皮糖蛋白水平明显高于健康受试者。在体外研究中，HCMV感染诱导人胶质母细胞瘤U87 MG（U87）细胞和人脐静脉内皮细胞（HUVECs）中白细胞介素6和肿瘤坏死因子-α的表达。此外，在HCMV感染的U87细胞和HUVECs中也观察到内皮糖蛋白水平升高，用更昔洛韦进行抗病毒治疗可降低内皮糖蛋白表达。这些结果表明，HCMV感染通过上调内皮糖蛋白和分泌炎性细胞因子导致胶质瘤进展。因此，抗HCMV治疗可能代表一种潜在的新型胶质瘤治疗策略。
