Editors' ChoiceMedulloblastoma

Going Viral

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Science Translational Medicine  12 Oct 2011:
Vol. 3, Issue 104, pp. 104ec167
DOI: 10.1126/scitranslmed.3003284

Viruses are clever microbes that flourish by evading a host’s defenses, but some viral survival strategies can be oncogenic. Indeed, the human cytomegalovirus (HCMV), a beta herpesvirus, has indirectly been implicated in multiple human cancers, including malignant glioma and colon and prostate cancers.

Medulloblastoma is the most common malignant brain tumor in children. Treatment options typically entail a combination of surgery and chemotherapy that can leave the patient with severe physical or neuropsychological damage. The inflammatory mediator PGE2, a COX-2 metabolite, has been implicated as a stimulatory growth factor that drives medulloblastoma progression. Interestingly, the HCMV protein US28 is a chemokine receptor homolog that induces COX-2 expression. Therefore, Baryawno and colleagues hypothesized that HCMV could be involved in medulloblastoma oncogenesis.

Baryawno et al. examined 37 primary medulloblastoma tumors for the presence of HCMV protein using immunohistochemistry or indirect immunofluorescence. Notably, 92% of these tumors expressed HCMV immediate-early (IE) proteins, and 73% expressed late-phase proteins. These data were confirmed by using flow cytometric analyses as well as polymerase chain reaction (PCR) to verify that the HCMV was not a contaminant of four commonly used laboratory strains. Next, eight publically available human medulloblastoma cell lines were analyzed with PCR. Evidence of HCMV infection was present in all cell lines, although fluorescence in situ hybridization analyses revealed no chromosomal integration of HCMV DNA. Furthermore, HCMV infection induced COX-2 and PGE2 in medulloblastoma cells. Indeed, both in vitro and in vivo studies confirmed that tumor growth was significantly impaired by combined treatment with the antiviral drug ganciclovir and the COX-2 inhibitor celecoxib.

The data presented suggest that HCMV can modulate the tumor environment and further the argument for the oncogenic potential of viruses. The mechanistic insights made in this study suggest new potential treatments of HCMV-infected medulloblastomas, including antivirals and anti-inflammatory agents, as well as provide HCMV as a new target for vaccine development for this devastating disease.

N. Baryawno et al., Detection of human cytomegalovirus in medulloblastomas reveals a potential therapeutic target. J. Clin. Invest. 121, 4043–4055 (2011). [Full Text]

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