SAN DIEGO — Some self-renewing stem cells may be a prime culprit in prostate cancer, and a certain gene in these cells contributes to the malignancy, suggests research reported February 20 at the annual meeting of the American Association for the Advancement of Science. Prostate cancer is the most common malignancy in men in the Western world, affecting one in six men.
“Think about cancer as a disease of stem cells,” said study coauthor Owen Witte, a Howard Hughes Medical Institute investigator at the University of California, Los Angeles. Mutations in these cells can cause “normal stem cells to lose their regularized behavior and instead turn into an incipient cancer,” he said.
Like many other tissues in the body, prostate tissue is made up of several different kinds of cells, including a class called basal stem cells. Normally these cells divide to replenish prostate tissue, but sometimes they become cancerous. Instead of producing normal cells, these stem cells lead to tumors.
“When we apply stem cell thinking to cancer, we find that in the run-up to cancer — the premalignant period — many, many genetic and heritable changes occur in the line of stem cells,” commented stem cell biologist Irving Weissman of Stanford University.
Witte and his colleagues wanted to determine in which class of cells prostate cancer originates in mice. The researchers separated mouse prostate cells into different groups based on type, introduced mutations often found in prostate cancers, and then implanted the cells back into mice one type at a time. Basal stem cells outpaced the other groups by far in their cancer-forming ability, the researchers reported February 9 in the Proceedings of the National Academy of Sciences. Evidence from earlier studies suggests that this might be happening in human prostate cancers, too.
In all cases the team has looked at, Witte said, the basal stem cells are what drive the cancer, regardless of the type of mutation.
A gene called Bmi-1 is important for these cells’ self-renewal and may also play a role in malignancy. When Bmi-1 activity was knocked down in basal stem cells, the cells were no longer able to self-renew, nor did they form tumors, Witte reported at the meeting.
“We get a dramatic change in the rate of growth and the tumor outcome by blocking this one single pathway,” Witte said. “I don’t think this will be a magic bullet to cure prostate cancer by any means, but it’s certainly a pathway that should be explored.”