Selection of a highly invasive neuroblastoma cell population through long-term human cytomegalovirus infection

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 
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.
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Metadaten
Author:Martin Michaelis, Susanne Barth, Rainer Breitling, Jochen Bruch, Daniela Steinberger, Florian Rothweiler, Karl Hackmann, Evelyn Schröck, Hans Wilhelm Doerr, Darren K. Griffin, Jindrich Cinatl, Jindrich Cinatl
URN:urn:nbn:de:hebis:30:3-242432
DOI:http://dx.doi.org/doi:10.1038/oncsis.2012.10
ISSN:2157-9024
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=23552602
Parent Title (English):Oncogenesis
Publisher:Nature Publishing Group
Place of publication:Basingstoke
Document Type:Article
Language:English
Date of Publication (online):2012/06/08
Date of first Publication:2012/04/30
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2012/06/08
Tag:cancer cell malignancy; human cytomegalovirus; long-term infection; neuroblastoma; oncomodulation
Volume:1
Issue:e10
Pagenumber:8
First Page:1
Last Page:8
Note:
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/
HeBIS PPN:303189517
Institutes:Erziehungswissenschaften
Medizin
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung-Keine kommerzielle Nutzung-Weitergabe unter gleichen Bedingungen

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