Researchers at the University of Pennsylvania School of Medicine have identified a link between a critical cancer pathway and an Epstein-Barr Virus (EBV) protein known to be expressed in a number of EBV-associated cancers. Their findings demonstrate a new mechanism by which EBV transforms human B cells from the immune system into cancerous cells, which can lead to development of B-cell lymphomas.
Erle S. Robertson, PhD, Associate Professor of Microbiology and Director of Tumor Virology, with Penn’s Abramson Cancer Center and MD/PhD student Jason Knight, published their results in the early March issue of Molecular and Cellular Biology.
Using human cell cultures infected with the Epstein-Barr virus, the investigators found that a specific viral protein targets a molecule that normally regulates the cell-cycle progression, or duplication process, of resting B cells. In the presence of this viral protein – called EBNA3C (for EBV nuclear antigen) – the cell cycle of the usually quiescent human B cells gets a jump start, which ultimately initiates uncontrolled growth.
EBV, a member of the herpesvirus family and one of the most common human viruses, plays a role in cancers such as lymphoproliferative diseases in transplant or AIDS patients, Burkitt’s lymphoma, Hodgkin’s lymphoma, and nasopharyngeal carcinoma, and also causes the well-known disease, infectious mononucleosis. As many as 95 percent of adults 20 years and older have been infected with EBV, but show no symptoms.
“Viruses that are associated with cancers typically target the cell cycle to gain control,” says Robertson. “However, this is the first time that laboratory research into how EBV drives the cancer process has directly identified a critical component of the cell cycle for control. Now we can develop targeted therapeutics to disrupt the function of this viral protein.” The researchers surmise that the first use of future therapies from these studies will be in lymphoproliferative disease in transplant and immunocompromised patients because this is a clear case of EBV-driven B-cell lymphoma.
The use of peptides to block the interaction between this essential EBV protein and the specific pathway in human B cells is currently underway. Initial studies show that the growth of EBV-associated cancer cells can be inhibited in tissue-culture assays. The investigators are actively pursuing this line of investigation for developing potential therapies.
This research was funded by the National Institutes of Health and the Leukemia and Lymophoma Society of America. Nikhil Sharma, a student from Cherokee High School, New Jersey who volunteers at Penn, was also a co-investigator in this study.