Vienna, Austria — A recent study suggests that the development of melanoma results in expression of retroviral genes and production of retroviral particles, neither of which are found in normal melanocytes or other tissues.
Vienna, Austria - A recent study suggests that the development of melanoma results in expression of retroviral genes and production of retroviral particles, neither of which are found in normal melanocytes or other tissues.
"It appears somehow that during the process of transformation, the viruses are activated and evolve from the melanoma cells," says Thomas Muster, Ph.D., associate professor, department of dermatology, University of Vienna Medical School and CEO of Green Hills Biotechnology.
"All melanoma cells expressed the viral proteins," Dr. Muster explains. "For example, the envelope protein of the virus is expressed on the cell surface before the virus particle forms. It uses part of the cell's envelope for its own envelope. That means that all the cells are somehow marked with retroviral proteins. So these retroviral proteins represent tumor markers."
While the common tumor marker GP 100 is present in only about 20 percent of melanoma cells, Dr. Muster adds that based on a separate analysis of hundreds of samples "we recently found that more than 90 percent of all melanoma patients have these retroviruses. We don't know whether these viruses are important for the development of melanoma. But (their presence) can provide the basis for development of a therapy against melanoma based on these retroviral proteins and also for diagnosis of melanoma."
In addition to the presence of retroviral proteins, Dr. Muster and his colleagues have detected antibodies against them in virtually all patients.
"If one checks whether a patient's sera are reactive to these retroviral proteins, one might be able to say whether the patient has melanoma or not," he says.
Retroviral proteins also may, one day, provide clearer information for the direction of treatment.
"It's a similar problem, because most tumor markers are only present in smaller percentages. This makes it difficult to attack the tumor. If only a small percentage of patients even have these markers, therapy directed at them is likely to fail. In our case, we know that approximately 90 percent of melanomas contain these markers, so success from that standpoint is much more likely. Therefore, one focus of our work now is to make antibodies against the retrovirus and check whether they might be used not only for diagnosis, but also for therapy," he says.
As for the pathogenesis of melanoma, recent research provides intriguing clues that Dr. Muster's approach might be valid. One study showed that in a mouse melanoma system, also known to express retroviral particles, suppressing this expression stops tumor growth (Mangeney M et al. Cancer Res 2005 April 1;65(7):2588-2591.). In the future, Dr. Muster and his colleagues will examine whether the same thing happens in humans.
"If we can show that the situation is similar in humans," he says, "it would provide support for our hypothesis that one can attack melanoma cells by targeting their retroviral proteins."
In the nearer term, Dr. Muster and his colleagues were working at press time to add more stage 1 and 2 melanoma samples to their data because such samples were underrepresented in their initial research.