Detection of human cytomegalovirus in medulloblastomas reveals a potential therapeutic target

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

Medulloblastomas are the most common malignant brain tumors in children. They express high levels of COX-2 and produce PGE(2), which stimulates tumor cell proliferation. Human cytomegalovirus (HCMV) is prevalent in the human population and encodes proteins that provide immune evasion strategies and promote oncogenic transformation and oncomodulation. In particular, HCMV induces COX-2 expression; STAT3 phosphorylation; production of PGE2, vascular endothelial growth factor, and IL-6; and tumor formation in vivo. Here, we show that a large proportion of primary medulloblastomas and medulloblastoma cell lines are infected with HCMV and that COX-2 expression, along with PGE2 levels, in tumors is directly modulated by the virus. Our analysis indicated that both HCMV immediate-early proteins and late proteins are expressed in the majority of primary medulloblastomas. Remarkably, all of the human medulloblastoma cell lines that we analyzed contained HCMV DNA and RNA and expressed HCMV proteins at various levels in vitro. When engrafted into immunocompromised mice, human medulloblastoma cells induced expression of HCMV proteins. HCMV and COX-2 expression correlated in primary tumors, cell lines, and medulloblastoma xenografts. The antiviral drug valganciclovir and the specific COX-2 inhibitor celecoxib prevented HCMV replication in vitro and inhibited PGE2 production and reduced medulloblastoma tumor cell growth both in vitro and in vivo. Ganciclovir did riot affect the growth of HCMV-negative tumor cell lines. These findings imply an important role for HCMV in medulloblastoma and suggest HCMV as a novel therapeutic target for this tumor.

Detaljer

Författare
  • Ninib Baryawno
  • Afsar Rahbar
  • Nina Wolmer-Solberg
  • Chato Taher
  • Jenny Odeberg
  • Anna Darabi
  • Zahidul Khan
  • Baldur Sveinbjornsson
  • O. -M. Fuskevag
  • Lova Segerstrom
  • Magnus Nordenskjold
  • Peter Siesjö
  • Per Kogner
  • John Inge Johnsen
  • Cecilia Soderberg-Naucler
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Kirurgi
  • Neurologi
Originalspråkengelska
Sidor (från-till)4043-4055
TidskriftJournal of Clinical Investigation
Volym121
Utgivningsnummer10
StatusPublished - 2011
PublikationskategoriForskning
Peer review utfördJa

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