Scientists identify prostate cancer cell of origin

UCLA scientists say they have identified for the first time a cell-of-origin for human prostate cancer, a discovery that could result in better predictive and diagnostic tools and the development of more effective targeted treatments for the disease.

The researchers, from UCLA’s Jonsson Comprehensive Cancer Center, proved that basal cells found in benign prostate tissue could become human prostate cancer in mice with suppressed immune systems, a finding that bucks conventional wisdom. It had been widely believed that luminal cells found in the prostate were the culprits behind prostate cancer because the resulting malignancies closely resembled luminal cells, said senior author Owen Witte, MD, of Jonsson Cancer Center and the UCLA Broad Stem Cell Research Center.

"Certainly the dominant thought is that human prostate cancer arose from the luminal cells because the cancers had more features resembling luminal cells," said Dr. Witte. "But we were able to start with a basal cell and induce human prostate cancer and now, as we go forward, this gives us a place to look in understanding the sequence of genetic events that initiates prostate cancer and defining the cell-signaling pathways that may be at work fueling the malignancy, helping us to potentially uncover new targets for therapy."

The researchers took healthy tissue from prostate biopsies and separated the cells based on their surface marker expression into groups of luminal cells and groups of basal cells. Using viral vectors as vehicles, they then expressed altered genes known to cause cancer into both cell populations and placed the cells in mice to see which developed cancer, said first author Andrew Goldstein of UCLA.

"Because of the widespread belief that luminal cells were the root of human prostate cancer, it would have been those cells examined and targeted to treat the disease," Goldstein said. "This study tells us that basal cells play an important role in the prostate cancer development process and should be an additional focus of targeted therapies."

Results from the study were published in Science (2010; 329:568-71).