Elsevier

Translational Research

Volume 177, November 2016, Pages 113-126
Translational Research

Original Article
Human cytomegalovirus infection contributes to glioma disease progression via upregulating endocan expression

https://doi.org/10.1016/j.trsl.2016.06.008Get rights and content
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open access

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.

Abbreviations

HCMV
human cytomegalovirus
U87
human glioblastoma U87 MG cells
HUVECs
human umbilical vein endothelial cells
GBM
glioblastoma multiforme
VEGF
vascular endothelial growth factor
VECs
vascular endothelial cells
GCV
ganciclovir
FBS
fetal bovine serum
IL-6
interleukin-6
TNF-α
tumor necrosis factor (TNF)-alpha
MTT
3-(4,5-dimethylthiazol-2-yl)-diphenyltetrazolium bromide
IHC
immunohistochemistry
ISH
in situ hybridization
ELISA
enzyme-linked immunosorbent assay
HGG
high-grade glioma
LGG
low-grade glioma
dpi
days post infection
HGF/SF
hepatocyte growth factor/scatter factor
IFN-γ
interferon gamma
STAT3
signal transducers and activators of transcription 3
NF-κB
nuclear factor κB

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Yan Xing and Yisong Wang contributed equally to this work.