title: Human cytomegalovirus infection contributes to glioma disease progression via upregulating endocan expression.
abstract: 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.
authors.affiliation: Department of Microbiology and Parasitology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xing
authors.affiliation: Department of Microbiology and Parasitology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
authors.forename: Yisong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Microbiology and Parasitology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
authors.forename: Shijie
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Microbiology and Parasitology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Microbiology and Parasitology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
authors.forename: Dongying
authors.initials: D
authors.lastname: Fan
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. Electronic address: dabiaozhou@163.com.
authors.forename: Dabiao
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Department of Microbiology and Parasitology, School of Basic Medical Sciences, Capital Medical University, Beijing, China; Center of Epilepsy, Beijing Institute for Brain Disorders, Beijing, China. Electronic address: anjing@ccmu.edu.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: An
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology / Q000821:virology*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002648:Child; D016207:Cytokines / Q000378:metabolism; D003587:Cytomegalovirus / Q000187:drug effects / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000150:complications* / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D018450:Disease Progression; D005260:Female; D015774:Ganciclovir / Q000494:pharmacology / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005910:Glioma / Q000235:genetics / Q000473:pathology / Q000821:virology*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D011509:Proteoglycans / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics*; D014763:Viral Matrix Proteins / Q000378:metabolism; D055815:Young Adult
chemical_list: D016207:Cytokines; C101134:ESM1 protein, human; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D011509:Proteoglycans; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa; D015774:Ganciclovir