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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.
AuthorsNina Wolmer-Solberg, Ninib Baryawno, Afsar Rahbar, Dieter Fuchs, Jenny Odeberg, Chato Taher, Vanessa Wilhelmi, Jelena Milosevic, Abdul-Aleem Mohammad, Tommy Martinsson, Baldur Sveinbjörnsson, John Inge Johnsen, Per Kogner, Cecilia Söderberg-Nauclér
JournalInternational journal of cancer (Int J Cancer) Vol. 133 Issue 10 Pg. 2351-61 (Nov 15 2013) ISSN: 1097-0215 [Electronic] United States
PMID23661597 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2013 UICC.
Chemical References
  • AC133 Antigen
  • Antigens, CD
  • Antiviral Agents
  • CD44 protein, human
  • Glycoproteins
  • Hyaluronan Receptors
  • PROM1 protein, human
  • Peptides
  • Prom1 protein, mouse
  • Ganciclovir
Topics
  • AC133 Antigen
  • Animals
  • Antigens, CD (metabolism)
  • Antiviral Agents (pharmacology, therapeutic use)
  • Cell Line
  • Cell Line, Tumor
  • Child
  • Child, Preschool
  • Cytomegalovirus (drug effects)
  • Cytomegalovirus Infections (complications, drug therapy)
  • Drug Delivery Systems
  • Female
  • Ganciclovir (pharmacology, therapeutic use)
  • Glycoproteins (metabolism)
  • Humans
  • Hyaluronan Receptors (metabolism)
  • Infant
  • Infant, Newborn
  • Male
  • Mice
  • Mice, Nude
  • Neuroblastoma (drug therapy, metabolism, virology)
  • Peptides (metabolism)
  • Prevalence
  • Random Allocation
  • Xenograft Model Antitumor Assays

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