A single adult stem cell from the prostate of a mouse can develop into an entire functional organ, scientists reported online yesterday in Nature. The finding proves that a population of stem cells exists in the adult prostate, as many have long suspected, and it could provide insight into how prostate cancer develops.
“It’s extremely exciting, the concept that you can reconstitute an entire prostate from a single cell,” says Tyler Jacks, director of the David H. Koch Institute for Integrative Cancer Research, at MIT, who was not involved in the work. “That’s impressive stuff.”
Unlike embryonic stem cells, which can potentially develop into any cell type in the body, adult stem cells are tissue-specific. Many organs are believed to house populations of adult stem cells, but in most cases their existence remains unproven. Known adult stem cells, however, can give rise to all the cell types that characterize the organs in which they’re found.
To sift out potential adult prostate stem cells, researchers at Genentech, in San Francisco, zeroed in on a group of cell-surface markers associated with suspected prostate stem cells. Since many of these markers are individually unreliable and poorly understood, the researchers tested a new one as well: a receptor protein called c-kit, which is known to be associated with other types of stem cells.
Using c-kit and three other markers, the researchers, led by senior scientist Wei-Qiang Gao, isolated a small population of likely stem cells from the prostates of mice. But while markers can point to candidates, they can’t unequivocally prove the identity of a stem cell. The cell still needs to demonstrate the capacity to develop into an entire organ.
To test for that capacity, Gao and his colleagues grafted individual stem-cell candidates onto the kidneys of living mice. In order to provide necessary developmental cues, they transferred, along with each cell, some connective cells from the urogenital cavities of rats. Three months later, the researchers removed the kidneys and analyzed the fate of the grafted cells. Of the 97 single-cell transplants, 14 had grown into fully functioning prostates–complete with multiple cell types, characteristic branching structures, and prostate-specific proteins.
Other groups have grown prostates in living mice from clumps of cells, but never before from a single cell. “That’s really the gold standard–that there’s an adult, tissue-specific stem cell,” says Scott Cramer, an associate professor of cancer biology at Wake Forest University School of Medicine, who was not involved in the study. The only other solid tissue for which this feat has been accomplished is the breast: a single breast stem cell can develop into an entire mammary gland.
Adult stem cells have been touted for their promise in regenerative medicine. But there is no clinical reason to regrow a prostate, says Leisa Johnson, a senior scientist at Genentech and coauthor of the Nature paper. The vast majority of prostate-cancer patients are beyond their child-bearing years, and the main side effects of prostate removal–urinary incontinence and impotence–are caused by nerve disruption during surgery, so they wouldn’t be remedied by a new prostate.
Even so, says Jacks, the newly isolated prostate stem cells may provide insight into adult stem cells in general. “Our understanding of stem cells–and adult stem cells in particular–might allow us to re-create damaged tissues that are lost during debilitating diseases,” he says.
More important, however, the stem cells may have much to reveal about prostate cancer. Only a small number of cells in a tumor actually have the capacity to spawn an entire tumor, with all its various cell types. Many researchers speculate that these cells, dubbed cancer stem cells or cancer-initiating cells, have much in common with normal adult stem cells. Some even suspect that cancer stem cells and normal stem cells are one and the same.
“We now believe that for many types of cancer, the cell that gives rise to the cancer in the normal tissue is itself a stem cell,” says Jacks. “If that is true for prostate cancer, then having the ability to purify and therefore study the normal stem cell would be an important tool in understanding how prostate cancer originates.”
Johnson agrees. “By gaining insights into the normal stem cell of the prostate, our hope is to gain better understanding of the cancer-initiating cell,” she says.
If it does turn out that stem cells, or stemlike cells, are responsible for triggering prostate cancer, markers like c-kit may also point the way to potential treatments. Now that the Genentech researchers have a pool of definitive prostate stem cells on hand, they can revise the catalogue of known prostate stem-cell markers and even begin to define their function. If any markers turn out to be essential for stem-cell proliferation, they would be ideal drug targets.
Characterizing the newly discovered prostate stem cells may also produce better ways to detect prostate cancer. “These cells could easily turn out to be the cells of origin for prostate cancer,” says Jacks, “and if you’re interested in early detection, it is important to understand where these cancers come from.”
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