title: Frequent detection of human cytomegalovirus in neuroblastoma: a novel therapeutic target?
abstract: Neuroblastoma is the most common and deadly tumor of childhood, where new therapy options for patients with high-risk disease are highly warranted. Human cytomegalovirus (HCMV) is prevalent in the human population and has recently been implicated in different cancer forms where it may provide mechanisms for oncogenic transformation, oncomodulation and tumor cell immune evasion. Here we show that the majority of primary neuroblastomas and neuroblastoma cell lines are infected with HCMV. Our analysis show that HCMV immediate-early protein was expressed in 100% of 36 primary neuroblastoma samples, and HCMV late protein was expressed in 92%. However, no infectious virus was detected in primary neuroblastoma tissue extracts. Remarkably, all six human neuroblastoma cell lines investigated contained CMV DNA and expressed HCMV proteins. HCMV proteins were expressed in neuroblastoma cells expressing the proposed stem cell markers CD133 and CD44. When engrafted into NMRI nu/nu mice, human neuroblastoma cells expressed HCMV DNA, RNA and proteins but did not produce infectious virus. The HCMV-specific antiviral drug valganciclovir significantly reduced viral protein expression and cell growth both in vitro and in vivo. These findings indicate that HCMV is important for the pathogenesis of neuroblastoma and that anti-viral therapy may be a novel adjuvant treatment option for children with neuroblastoma.
authors: Department of Medicine, Center for Molecular Medicine, Karolinska University Hospital in Solna, Karolinska Institutet, Stockholm, Sweden.
authors: Nina
authors: N
authors: Wolmer-Solberg
authors: Ninib
authors: N
authors: Baryawno
authors: Afsar
authors: A
authors: Rahbar
authors: Dieter
authors: D
authors: Fuchs
authors: Jenny
authors: J
authors: Odeberg
authors: Chato
authors: C
authors: Taher
authors: Vanessa
authors: V
authors: Wilhelmi
authors: Jelena
authors: J
authors: Milosevic
authors: Abdul-Aleem
authors: AA
authors: Mohammad
authors: Tommy
authors: T
authors: Martinsson
authors: Baldur
authors: B
authors: Sveinbjörnsson
authors: John Inge
authors: JI
authors: Johnsen
authors: Per
authors: P
authors: Kogner
authors: Cecilia
authors: C
authors: Söderberg-Nauclér
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D002460:Cell Line; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D003587:Cytomegalovirus / Q000187:drug effects*; D003586:Cytomegalovirus Infections / Q000150:complications* / Q000188:drug therapy; D016503:Drug Delivery Systems; D005260:Female; D015774:Ganciclovir / Q000494:pharmacology / Q000627:therapeutic use; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology*; D010455:Peptides / Q000378:metabolism; D015995:Prevalence; D011897:Random Allocation; D023041:Xenograft Model Antitumor Assays
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D000998:Antiviral Agents; C497483:CD44 protein, human; D006023:Glycoproteins; D018960:Hyaluronan Receptors; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D015774:Ganciclovir
keywords: human cytomegalovirus; neuroblastoma; valganciclovir