In work that has the potential to affect prostate cancer research worldwide, Hopkins scientists have discovered that many prostate cancer cells lines, cultivated and sold to laboratories, may be contaminated with mouse viruses. These viruses are “actively replicating and infectious gammaretroviruses,” says pathologist Angelo De Marzo, M.D., Ph.D., who made the discovery with scientist Karen Sfanos, Ph.D. Their work was published in PLoS ONE.
“The major implications of this work are that hundreds, if not thousands of biological cancer research-related studies have been carried out with these cell lines,” says De Marzo. “It is distinctly possible that some, if not many, of the results of these studies could have been affected in unforeseeable ways by the presence of these heretofore unknown mouse viruses.”
The discovery was made while De Marzo and Sfanos (a postdoctoral fellow in De Marzo’s lab, who has since joined the faculty), along with investigators from the National Cancer Institute, were hunting for a particular virus called XMRV. In 2006, researchers worldwide became very excited when XMRV, related to the mouse leukemia virus, was isolated in some human prostate tumor tissues. There was good reason to believe that this virus might be a cause of prostate cancer in some men — particularly in light of the landmark finding by geneticist William B. Isaacs, Ph.D. Isaacs, The William Thomas Gerrard, Mario Anthony Duhon, and Jennifer and John Chalsty Professor of Urology, discovered that men who inherit a specific mutation in a gene called RNASEL are more prone to prostate cancer. The RNASEL gene’s job is to fight off viruses, and when it is mutated, the body is more vulnerable to invading viruses.
Sfanos, then working with Isaacs as a graduate student, began looking for this virus in patient specimens housed at Hopkins. She didn’t find it. Sfanos investigated 338 tissue samples from 200 patients, and her study, published in Prostate, was the first to report the complete absence of XMRV in prostate cancer. In 2010, De Marzo was approached by Alan Rein, Ph.D., a well-known retrovirus scientist at the NCI, who wanted to pursue the possible role of XMRV as a cause of prostate cancer. De Marzo, Sfanos, Rein and the NCI’s Amanda Aloia, Ph.D., also showed a complete absence of the virus in prostate cancer tissues. The team studied 800 more prostate cancer tissue samples in exhaustive detail, using novel antibodies and a new polymerase chain reaction-based approach. Their work was recently published in Cancer Research.
How to explain the team’s determination of absolutely no XMRV in the prostate? “A number of recent papers have shown that the presence of XMRV in patient samples is likely the result of laboratory contamination,” says De Marzo, “and two papers just published in Science refute the plausibility that this virus even circulates in the human population. It appears to have been created by accident in the laboratory during the cultivation of human prostate cancer tumors in certain mouse strains.”
De Marzo and Sfanos’s discovery of the mouse virus-contaminated prostate cell lines emphasizes the inherent danger of working with human cancer cell lines that have previously been grown in laboratory mice. “It is critical for researchers to test their cell lines for contamination with these viruses,” cautions De Marzo, “to avoid the potential confounding of their experimental results as well as the potential to cross-contaminate other cell lines in their labs.”
“ Hundreds, if not thousands
of biological cancer researchrelated
studies have been carried
out with these cell lines. It is
distinctly possible that some, if
not many, of the results of these
studies could have been affected
in unforeseeable ways.”