Thursday, October 23, 2008

Prostates Grown from Stem Cells

New proof that the mouse prostate contains stem cells could aid cancer research.

By Jocelyn Rice

Presto prostate: Three months after a single prostate stem cell was grafted onto this mouse kidney (pink), it has grown into a fully functioning prostate (white). Now researchers know for sure that the prostate contains adult stem cells, each capable of building a prostate from scratch. By characterizing those cells, they hope to shed light on the stem-cell-like beginnings of prostate cancer and to help improve detection and treatment methods. Credit: Kevin G. Leong et al., Nature

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.