Please use this identifier to cite or link to this item: https://doi.org/10.18632/oncotarget.9722
Title: Human cytomegalovirus may promote tumour progression by upregulating arginase-2
Authors: Costa, H
Xu, X
Overbeek, G
Vasaikar, S
Pawan K. Patro, C
Kostopoulou, O.N
Jung, M
Shafi, G
Ananthaseshan, S
Tsipras, G
Davoudi, B
Mohammad, A.-A
Lam, H
Strååt, K
Wilhelmi, V
Shang, M
Tegner, J
Tong, J.C 
Wong, K.T
Söderberg-Naucler, C
Yaiw, K.-C
Keywords: arginase
arginase 2
gelatinase A
gelatinase B
hydrolase inhibitor
n (omega) hydroxy nor arginine
nitric oxide synthase
small interfering RNA
unclassified drug
vasculotropin
arginase
Article
bioinformatics
cancer genetics
cancer growth
cancer survival
cancer tissue
cell invasion
cell migration
cell proliferation
cellular parameters
controlled study
enzyme activity
enzyme induction
enzyme regulation
ex vivo study
glioblastoma
glioblastoma cell line
human
human cell
Human cytomegalovirus
human tissue
immunohistochemistry
in vitro study
nonhuman
protein expression
upregulation
vasculogenic mimicry
virus carcinogenesis
virus cell interaction
biosynthesis
carcinogenesis
cell motion
Cytomegalovirus
cytomegalovirus infection
disease exacerbation
enzymology
genetic transfection
genetics
glioblastoma
metabolism
neovascularization (pathology)
pathology
physiology
tumor cell line
vascularization
virology
Arginase
Carcinogenesis
Cell Line, Tumor
Cell Movement
Cell Proliferation
Cytomegalovirus
Cytomegalovirus Infections
Disease Progression
Glioblastoma
Humans
Immunohistochemistry
Neovascularization, Pathologic
Transfection
Up-Regulation
Issue Date: 2016
Citation: Costa, H, Xu, X, Overbeek, G, Vasaikar, S, Pawan K. Patro, C, Kostopoulou, O.N, Jung, M, Shafi, G, Ananthaseshan, S, Tsipras, G, Davoudi, B, Mohammad, A.-A, Lam, H, Strååt, K, Wilhelmi, V, Shang, M, Tegner, J, Tong, J.C, Wong, K.T, Söderberg-Naucler, C, Yaiw, K.-C (2016). Human cytomegalovirus may promote tumour progression by upregulating arginase-2. Oncotarget 7 (30) : 47221-47231. ScholarBank@NUS Repository. https://doi.org/10.18632/oncotarget.9722
Rights: Attribution 4.0 International
Abstract: Background: Both arginase (ARG2) and human cytomegalovirus (HCMV) have been implicated in tumorigenesis. However, the role of ARG2 in the pathogenesis of glioblastoma (GBM) and the HCMV effects on ARG2 are unknown. We hypothesize that HCMV may contribute to tumorigenesis by increasing ARG2 expression. Results: ARG2 promotes tumorigenesis by increasing cellular proliferation, migration, invasion and vasculogenic mimicry in GBM cells, at least in part due to overexpression of MMP2/9. The nor-NOHA significantly reduced migration and tube formation of ARG2-overexpressing cells. HCMV immediate-early proteins (IE1/2) or its downstream pathways upregulated the expression of ARG2 in U-251 MG cells. Immunostaining of GBM tissue sections confirmed the overexpression of ARG2, consistent with data from subsets of Gene Expression Omnibus. Moreover, higher levels of ARG2 expression tended to be associated with poorer survival in GBM patient by analyzing data from TCGA. Methods: The role of ARG2 in tumorigenesis was examined by proliferation-, migration-, invasion-, wound healing- and tube formation assays using an ARG2- overexpressing cell line and ARG inhibitor, N (omega)-hydroxy-nor-L-arginine (nor-NOHA) and siRNA against ARG2 coupled with functional assays measuring MMP2/9 activity, VEGF levels and nitric oxide synthase activity. Association between HCMV and ARG2 were examined in vitro with 3 different GBM cell lines, and ex vivo with immunostaining on GBM tissue sections. The viral mechanism mediating ARG2 induction was examined by siRNA approach. Correlation between ARG2 expression and patient survival was extrapolated from bioinformatics analysis on data from The Cancer Genome Atlas (TCGA). Conclusions: ARG2 promotes tumorigenesis, and HCMV may contribute to GBM pathogenesis by upregulating ARG2.
Source Title: Oncotarget
URI: https://scholarbank.nus.edu.sg/handle/10635/179967
ISSN: 19492553
DOI: 10.18632/oncotarget.9722
Rights: Attribution 4.0 International
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