Cytomegalovirus contributes to glioblastoma in the context of tumor suppressor mutations.

Cancer research 2013 Jun 01

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To study the controversial role of cytomegalovirus (CMV) in glioblastoma, we assessed the effects of murine CMV (MCMV) perinatal infection in a GFAP-cre; Nf1(loxP/+); Trp53(-/+) genetic mouse model of glioma (Mut3 mice). Early on after infection, MCMV antigen was predominantly localized in CD45+ lymphocytes in the brain with active viral replication and local areas of inflammation, but, by 7 weeks, there was a generalized loss of MCMV in brain, confirmed by bioluminescent imaging. MCMV-infected Mut3 mice exhibited a shorter survival time from their gliomas than control Mut3 mice perinatally infected with mock or with a different neurotropic virus. Animal survival was also significantly shortened when orthotopic gliomas were implanted in mice perinatally infected with MCMV versus controls. MCMV infection increased phosphorylated STAT3 (p-STAT3) levels in neural stem cells (NSC) harvested from Mut3 mice subventricular zone, and, in vivo, there was increased p-STAT3 in NSCs in MCMV-infected compared with control mice. Of relevance, human CMV (HCMV) also increased p-STAT3 and proliferation of patient-derived glioblastoma neurospheres, whereas a STAT3 inhibitor reversed this effect in vitro and in vivo. These findings thus associate CMV infection to a STAT3-dependent modulatory role in glioma formation/progression in the context of tumor suppressor mutations in mice and possibly in humans. ©2013 AACR.

Citation

Richard L Price, Jieun Song, Katherine Bingmer, Tae Hyong Kim, Ji-Yeun Yi, Michal O Nowicki, Xiaokui Mo, Todd Hollon, Eric Murnan, Christopher Alvarez-Breckenridge, Soledad Fernandez, Balveen Kaur, Andreana Rivera, Michael Oglesbee, Charles Cook, E Antonio Chiocca, Chang-Hyuk Kwon. Cytomegalovirus contributes to glioblastoma in the context of tumor suppressor mutations. Cancer research. 2013 Jun 01;73(11):3441-50