Research
Print page Print page
Switch language
Rigshospitalet - a part of Copenhagen University Hospital
Published

Cytomegalovirus infection induces a stem cell phenotype in human primary glioblastoma cells: prognostic significance and biological impact

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. A novel neurodegenerative spectrum disorder in patients with MLKL deficiency

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Programming of adipose tissue miR-483-3p and GDF-3 expression by maternal diet in type 2 diabetes

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. p53-independent upregulation of miR-34a during oncogene-induced senescence represses MYC

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. TERT promoter mutations in primary and secondary WHO grade III meningioma

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. The Ki-67 Proliferation Index as a Marker of Time to Recurrence in Intracranial Meningioma

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Preoperative antibiotic prophylaxis regimen in brain tumour surgery in Sweden: a quasi-experimental study

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Return to work following diagnosis of low-grade glioma: A nationwide matched cohort study

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. Human RTEL1 associates with Poldip3 to facilitate responses to replication stress and R-loop resolution

    Research output: Contribution to journalJournal articleResearchpeer-review

  • O Fornara
  • J Bartek
  • A Rahbar
  • J Odeberg
  • Z Khan
  • I Peredo
  • P Hamerlik
  • J Bartek
  • G Stragliotto
  • N Landázuri
  • C Söderberg-Nauclér
View graph of relations

Glioblastoma (GBM) is associated with poor prognosis despite aggressive surgical resection, chemotherapy, and radiation therapy. Unfortunately, this standard therapy does not target glioma cancer stem cells (GCSCs), a subpopulation of GBM cells that can give rise to recurrent tumors. GBMs express human cytomegalovirus (HCMV) proteins, and previously we found that the level of expression of HCMV immediate-early (IE) protein in GBMs is a prognostic factor for poor patient survival. In this study, we investigated the relation between HCMV infection of GBM cells and the presence of GCSCs. Primary GBMs were characterized by their expression of HCMV-IE and GCSCs marker CD133 and by patient survival. The extent to which HCMV infection of primary GBM cells induced a GCSC phenotype was evaluated in vitro. In primary GBMs, a large fraction of CD133-positive cells expressed HCMV-IE, and higher co-expression of these two proteins predicted poor patient survival. Infection of GBM cells with HCMV led to upregulation of CD133 and other GSCS markers (Notch1, Sox2, Oct4, Nestin). HCMV infection also promoted the growth of GBM cells as neurospheres, a behavior typically displayed by GCSCs, and this phenotype was prevented by either chemical inhibition of the Notch1 pathway or by treatment with the anti-viral drug ganciclovir. GBM cells that maintained expression of HCMV-IE failed to differentiate into neuronal or astrocytic phenotypes. Our findings imply that HCMV infection induces phenotypic plasticity of GBM cells to promote GCSC features and may thereby increase the aggressiveness of this tumor.

Original languageEnglish
JournalCell Death and Differentiation
Volume23
Issue number2
Pages (from-to)261-9
Number of pages9
ISSN1350-9047
DOIs
Publication statusPublished - Feb 2016

ID: 46011481