TY  - JOUR
A1  - Michaelis, Martin
A1  - Barth, Susanne
A1  - Breitling, Rainer
A1  - Bruch, Jochen
A1  - Steinberger, Daniela
A1  - Rothweiler, Florian
A1  - Hackmann, Karl
A1  - Schröck, Evelin
A1  - Doerr, Hans Wilhelm
A1  - Griffin, Darren K.
A1  - Cinatl, Jindrich
A1  - Cinatl, Jindrich
T1  - Selection of a highly invasive neuroblastoma cell population through long-term human cytomegalovirus infection
T2  - Oncogenesis
N2  - The human cytomegalovirus (HCMV) is suspected to increase tumour malignancy by infection of cancer and/or stroma cells (oncomodulation). So far, oncomodulatory mechanisms have been attributed to the presence of HCMV and direct action of its gene products on cancer cells. Here, we investigated whether the prolonged presence of HCMV can result in the irreversible selection of a cancer cell population with increased malignancy. The neuroblastoma cell line UKF-NB-4 was long-term (200 passages) infected with the HCMV strain Hi91 (UKF-NB-4Hi) before virus eradication using ganciclovir (UKF-NB-4HiGCV). Global gene expression profiling of UKF-NB-4, UKF-NB-4Hi and UKF-NB-4HiGCV cells and subsequent bioinformatic signal transduction pathway analysis revealed clear differences between UKF-NB-4 and UKF-NB-4Hi, as well as between UKF-NB-4 and UKF-NB-4HiGCV cells, but only minor differences between UKF-NB-4Hi and UKF-NB-4HiGCV cells. Investigation of the expression of a subset of five genes in different chronically HCMV-infected cell lines before and after virus eradication suggested that long-term HCMV infection reproducibly causes specific changes. Array comparative genomic hybridisation showed virtually the same genomic differences for the comparisons UKF-NB-4Hi/UKF-NB-4 and UKF-NB-4HiGCV/UKF-NB-4. UKF-NB-4Hi cells are characterised by an increased invasive potential compared with UKF-NB-4 cells. This phenotype was completely retained in UKF-NB-4HiGCV cells. Moreover, there was a substantial overlap in the signal transduction pathways that differed significantly between UKF-NB-4Hi/UKF-NB-4HiGCV and UKF-NB-4 cells and those differentially regulated between tumour tissues from neuroblastoma patients with favourable or poor outcome. In conclusion, we present the first experimental evidence that long-term HCMV infection can result in the selection of tumour cell populations with enhanced malignancy.
KW  - human cytomegalovirus
KW  - neuroblastoma
KW  - oncomodulation
KW  - long-term infection
KW  - cancer cell malignancy
Y1  - 2012
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/24243
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-242432
SN  - 2157-9024
N1  - Oncogenesis is an open-access journal published by Nature Publishing Group. This work is licensed under the Creative Commons AttributionNonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
VL  - 1
IS  - e10
SP  - 1
EP  - 8
PB  - Nature Publishing Group
CY  - Basingstoke
ER  -