"Acne Bacteria," Chronic Inflammation, and Prostate Cancer
WA few years ago, when Karen Sfanos, Ph.D., the Beth W. and A. Ross Myers Scholar, was a graduate student in the laboratory of William Isaacs, Ph.D., the William Thomas Gerrard, Mario Anthony Duhon and Jennifer and John Chalsty Professor of Urology, she went to a meeting. Patrick Walsh, M.D., was also there, and the discussion centered around a recent report in the medical literature that a certain species of bacteria, P. acnes – the same kind of bacteria that plagues teenagers worldwide by causing acne – was found in prostate cancer specimens, and was more likely to be found in prostate tissue that also contained inflammation. Could a bacterial infection lead to prostate cancer? There is reason to believe that it might. A number of Hopkins scientists including Isaacs, Angelo De Marzo, M.D., Ph.D., William Nelson, M.D., Ph.D., and Elizabeth Platz, Sc.D., have been studying the possible link between bacterial infections and prostate cancer, alerted by pathologists who found unexplained inflammation and inflammation-associated tissue damage in biopsy samples and in prostate specimens examined after radical prostatectomy. Brady scientists have been at the forefront of those making these discoveries and asking further questions.
"As many as 20 percent of all human cancers are associated with infections, either as a direct cause or as a contributing factor," says Sfanos. In other words, maybe the infection itself does not cause cancer, but it leads long-term inflammation, and this creates a more hospitable environment that ultimately allows cancer to develop. With so many cases of cancer linked to infection, "this represents a significant global cancer burden, as well as a tremendous opportunity for cancer treatment and prevention strategies with antibiotics and vaccines."
But this particular form of bacteria? "It is ubiquitously present on human skin," and this has posed a problem for scientists trying to investigate it. Was it truly an infection within the prostate, or was there just some unintentional contamination of the bacterial culture from the skin or surgical environment? After that meeting, Sfanos studied prostate tissues from men undergoing treatment for prostate cancer and confirmed that P. acnes can indeed be cultured from prostate tissues; her findings were published in 2008 in The Prostate. With further encouragement from Isaacs and Walsh, Sfanos, now an assistant professor of pathology, has continued to study the potential of role of P. acnes as a cause of long-term inflammation that leads to prostate cancer.
In one recent study, Sfanos’s group used a new technique called MultiLocus Sequence Typing to categorize the types of P. acnes that they found in prostate tissue samples. "We found that the strains of P. acnes isolated from the human prostate are related to strains of P. acnes found in the male urinary tract, or found in opportunistic infections – as opposed to strains that are associated with severe acne." The results of this study, published in The Prostate, suggest that these prostate-growing strains do not simply represent contamination from the skin.
Maybe the infection itself does not
cause cancer, but leads to long-term
inflammation, and this ultimately
allows cancer to develop.
But exactly what these bacteria are doing in the prostate has been challenging to determine. To find out more, Sfanos and colleagues have turned to mice – specifically, to a mouse model of inflammation in the prostate developed using one of the P. acnes strains Sfanos isolated from human prostate tissue samples. "In our studies of prostate infections in mice, we have observed that a single bacterial infection can cause chronic prostate inflammation that persists for months after the initial infection," she says. Based on these and other findings, Sfanos believes that there may be a long lag time – years, or even decades – between an initial bacterial infection, the development of chronic inflammation, and the development of prostate cancer. These findings also were published in The Prostate.
With support from the Patrick C. Walsh Prostate Cancer Research Fund, Sfanos is now studying the long-term effects of different bacterial strains in infected mouse prostates, and evaluating the inflammation that these bacterial strains cause. "We aim to study the potential pathogenic effects of long-term infection and chronic inflammation for six months to a year, produced by different species of bacteria in infection models of the mouse prostate." Sfanos and colleagues are looking at blood and prostate tissue for inflammatory cytokines, cells made by the immune system, in hopes of learning more about how the body reacts to specific bacteria. "The ultimate translation of our studies would be to compare the inflammatory responses that we observe in mice to the inflammatory responses observed in the human prostate, and in human prostate cancer."