THE PATRICK C. WALSH PROSTATE CANCER RESEARCH FUND AWARDEES
Deadly Chain: Inflammation, Oxidative Damage, and Cancer
Inflammation causes harmful molecules, called "reactive oxygen species" to form. One such molecule is hydrogen peroxide. When the body makes enough of it, hydrogen peroxide can hurt cells, and cause oxidative damage — damage to DNA, which can lead to mutations, and then to cancer.
In the prostate, one molecule, when it reacts with oxygen, can churn out enough hydrogen peroxide to damage DNA. This oxidized molecule is called spermine, and molecular pharmacologist Robert Casero, Ph.D., the Irene and Bernard L. Schwartz Scholar, is very interested in the role this chemical and the enzyme, spermine oxidase, might play in prostate cancer. He and colleagues have recently shown that when stomach tissue is infected by H. pylori, a nasty form of bacteria — well-linked to inflammation, it's also known to cause stomach ulcers and, eventually, stomach cancer — spermine oxidase makes hydrogen peroxide. The result is DNA damage. "These findings may provide the link between H. pylori infection, inflammation, and gastric cancer," notes Casero. This process in stomach cancer, he continues, is eerily similar to what's happening in cells that are on the brink of becoming prostate cancer. They are in a condition called "proliferative inflammatory atrophy," a wild mix of cells first spotted under the microscope by Hopkins pathologists Angelo De Marzo and Jonathan Epstein — hotspots of inflammation, mixed with cells that appear to be dying, but are actually proliferating very rapidly.
These findings may provide the
"The prostate has the highest concentration of spermine of any human tissue," Casero reports. "We believe that inflammation-caused induction of spermine oxidase, and its resulting damage, has the potential to cause prostate cancer." Casero is working to nail down this link between spermine oxidase and the development of prostate cancer, studying tissue samples to see if there's a correlation between spermine oxidase expression and a man's stage and grade of prostate cancer. "We will also try to determine exactly how inflammation regulates spermine oxidase," and figure out whether the oxidative damage spermine oxidase produces is enough to cause prostate cancer.
"We hope our results will provide a link between chronic inflammation, hydrogen peroxide production, DNA damage and cancer-causing progression — and at the same time, provide a target for chemo-preventive intervention.