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Cytomegalovirus Might Speed Brain Cancer Growth

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Key Points

  • Cytomegalovirus, a virus that infects most middle-aged Americans, is often associated with glioblastoma, but whether it plays a role in the cancer is unknown.
  • This study indicates that murine cytomegalovirus can speed the tumor’s growth in mice when the tumor-suppressor genes p53 and NF1 are mutated in neural stem cells of the brain.
  • The findings suggest that viruses might influence cancer progression, and that antiviral therapy might improve the treatment of these aggressive brain tumors.

A study led by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) and Dana-Farber Cancer Institute suggests that cytomegalovirus, a virus that infects most adults in the United States, might significantly accelerate the development and progression of glioblastoma. The findings were published in the journal Cancer Research.

Although cytomegalovirus itself does not cause cancer, the study suggests that it might influence tumor development when changes occur that silence the p53 and Nf1 tumor-suppressor genes in tumor cells.

Cytomegalovirus

Some 50% to 80% of Americans become infected with cytomegalovirus by age 40 through contact with infected bodily fluids, but the virus remains dormant in most people.

“Cytomegalovirus has been detected in many cancer types, suggesting that it might be reactivated when cancer occurs in the body,” said co-corresponding author and researcher Chang-Hyuk Kwon, PhD, Assistant Professor of Neurological Surgery at OSUCCC – James and the Dardinger Center for Neuro-oncology and Neurosciences.

The researchers also learned that cytomegalovirus stimulates tumor-cell proliferation by activating the STAT3 signaling pathway, which plays an important role in controlling cell proliferation in healthy cells.

“Our data indicate that cytomegalovirus contributes to glioblastoma when already-mutated cancer cells proliferate using the STAT3 signaling pathway,” Dr. Kwon said. “We believe that cytomegalovirus’s action occurs in the tumor’s cells of origin early in tumor initiation.”

Mouse Models

Dr. Kwon and colleagues conducted the study using two mouse models infected with murine cytomegalovirus. One model developed glioblastoma spontaneously; the other received implants of human glioblastoma cells.

Researchers found that murine cytomegalovirus–infected mice with genetic mutations in p53 and NF1 in their brain cells predisposing them to spontaneous glioblastoma had shorter survival than noninfected mice with the same mutations. Significantly shorter survival compared with controls was also observed after implanting human gliomas into the brains of murine cytomegalovirus–infected animals.

Murine cytomegalovirus infection increased levels of activated STAT3 in neural stem cells, and human cytomegalovirus infection increased STAT3 activation. Human cytomegalovirus also increased STAT3 activation and proliferation of patient-derived glioblastoma cells, whereas a STAT3 inhibitor reversed this effect in cell and animal models.

Questions Raised

The findings raise questions about how cancer is studied, said co-corresponding author E. Antonio Chiocca, MD, PhD, Chairman of Neurosurgery at the Brigham and Women’s Hospital and Surgical Director for the Center for Neuro-oncology at Dana-Farber Cancer Institute in Boston.

“First, we usually study cancer in models that are virus-free, but our findings suggest that cytomegalovirus might play a significant role in human cancers,” he said.

“Secondly, antiviral therapy against cytomegalovirus might now be justified for human cancers, and immune responses to such cancer-modulating viruses should be carefully studied,” Dr. Chiocca added.

Funding from the NIH/National Institute of Neurological Disorders and Stroke (grants NS045758-06 and NS064607), the Dardinger Neuro-oncology Fund, and the Jeffrey Thomas Hayden Foundation supported this research.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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