First Evidence of Virus Link to Some Prostate Cancers
First Evidence of Virus Link to Some Prostate Cancers
Monday, 07 September 2009 00:00
A type of virus known to cause leukemia and sarcomas in animals has been found for the first time in human prostate cancer cells, according to researchers at the University of Utah and Columbia University medical schools. Their discovery may help in identifying a viral cause of prostate cancer.This would open opportunities for developing diagnostic tests, vaccines, and therapies for treating the cancer.
The researchers say they found the XMRV virus in almost a third of the prostate tumors they looked at.
"We found that XMRV was present in 27 percent of prostate cancers we examined and that it was associated with more aggressive tumors," said Ila R. Singh, M.D., Ph.D., associate professor of pathology at University of Utah and the study’s senior author. "We still don’t know that this virus causes cancer in people, but that is an important question we’re going to investigate."
Along with providing the first proof that XMRV is present in malignant cells, the study also confirmed that XMRV is a gammaretrovirus, a simple retrovirus first isolated from prostate cancers in 2006 by the researchers at the University of California, San Francisco (UCSF), and the Cleveland Clinic. Gammaretroviruses are known to cause cancer in animals, but have not been shown to do so in humans.
The new study compared benign (non-malignant) prostate tissues with prostate cancer tissues and found much higher rates of XMRV virus in malignant cells.
Singh's team examined more than 200 human prostate cancers, and compared them to more than 100 non-cancerous prostate tissues. They found 27 percent of the cancers contained XMRV, compared to only 6 percent of the benign tissues. The viral proteins were found almost exclusively in cancerous prostate cells, suggesting that XMRV infection may be directly linked to the formation of prostate tumors.
Retroviruses insert a DNA copy of their genome into the chromosomes of the cells they infect. This sometimes happens close by a gene that regulates cell growth, disrupting normal cell growth, resulting in more rapid proliferation of such a cell, which eventually develops into a cancer. This is how gammaretroviruses in general cause cancer. Singh is currently examining if a similar mechanism might be involved with XMRV and prostate cancer.
Previous research on possible links between XMRV (full name XMRV (Xenotropic murine leukemia virus-related virus) and prostate cancer included work showing that XMRV is a virus that can be attacked by immune system elements, notably interferon (IFN) and its helper chemicals (B. Dong, Robert H. Silverman et al, 2007). The Cleveland Clinic research focused on possible genetic links between XMRV and some familial prostate cancers.
Dr. Singh's results challenge the family connection. She and her colleagues showed that susceptibility to XMRV infection is not enhanced by a genetic mutation, as was previously reported. If XMRV were caused by the mutation, only the 10 percent of the population who carry the mutated gene would be at risk for infection with virus. But Singh found no connection between XMRV and the mutation, meaning the risk for infection may extend to the population at large.
While the study answers important questions about XMRV, it also raises a number of other questions, such as whether the virus infects women, is sexually transmitted, how prevalent it is in the general population, and whether it causes cancers in tissues other than the prostate.
"We have many questions right now," Singh said, "and we believe this merits further investigation."
Viruses have been shown to cause cancer of the cervix, connective tissues (sarcomas), immune system (lymphoma), and other organs. If the retrovirus is shown to cause prostate cancer, this could have important implications for preventing viral transmission and for developing vaccines to prevent XMRV infection in people.
CREDITS, LINKS AND SOURCES
Ila R. Singh, M.D., Ph.D., associate professor of pathology at University of Utah, is also a member of the U of U’s Huntsman Cancer Institute and associate medical director at ARUP Laboratories. She moved to Utah from Columbia University Medical Center in 2008, where she began this research. She remains an adjunct faculty member at Columbia.
ARUP Laboratories is a national clinical and anatomic pathology reference laboratory. Owned by the University of Utah, ARUP offers a menu of medical tests.
The study was scheduled for publication Sept. 7 online in the Proceedings of the National Academy of Sciences.We will update this link when it appears.
University of Utah Health Sciences
Fibrils of prostatic acid phosphatase fragments boost infections with XMRV (xenotropic murine leukemia virus-related virus), a human retrovirus associated with prostate cancer. Hong S, Silverman RH, et al. J Virol. 2009 Jul;83(14):6995-7003.
Prevalence of human gammaretrovirus XMRV in sporadic prostate cancer. Fischer N, Hellwinkel O, Schulz C, Chun FK, Huland H, Aepfelbacher M, Schlomm T.
J Clin Virol. 2008 Nov;43(3):277-83.
A new human retrovirus associated with prostate cancer.. Hung Fan, PNAS 2007.
An infectious retrovirus susceptible to an IFN antiviral pathway from human prostate tumors Beihua Dong et al.
