Led by Michael Shen, Ph.D., professor of medicine and genetics and development at Columbia University Medical Center, the researchers found the rare stem cells, called CARNs (which stands for "castration-resistant Nkx3.1-expressing cells"), within the ducts inside the mouse prostate.
The stem cells are involved in regenerating prostate tissue, but the researchers also found that CARNs can give rise to cancer if certain tumor suppressor genes in the cells are inactivated.
The findings will be published in an advance online edition of Nature at 1 p.m. ET on Wednesday, September 9, 2009.
Understanding which cells in the prostate give rise to cancer may help researchers develop better treatments for prostate cancer. But the identity of these cells of origin for prostate cancer has been controversial.
Recently, some researchers have proposed that prostate cancer may arise from normal adult stem cells, since stem and cancer cells share several characteristics. But the only stem cells previously described in the prostate are basal cells, which have been considered to form a "support" layer for the luminal cells that make prostate secretions. However, since prostate cancers are filled exclusively with cells that have features of luminal cells, it has been unclear how cancer might arise from basal cells.
The new study may resolve this conundrum because the newly discovered adult stem cells are also luminal cells. "Previous research suggested that prostate cancer originates from basal stem cells, and that during cancer formation these cells differentiate into luminal cells," said Dr. Shen. "Instead, CARNs may represent a luminal origin for prostate cancer."
And indeed, the researchers found that CARNs in mice can give rise to prostate cancers, after the cells lose the activity of PTEN, a gene that is frequently mutated in human prostate cancers.
The results do not mean, however, that CARNs give rise to "cancer stem cells," cells inside a tumor that are capable of regenerating the cancer from a single cell. "The relationship between the normal prostate stem cells and potential cancer stem cells is not known yet," said Dr. Shen. "And even the existence of cancer stem cells in prostate tumors is not established."
Also unclear is whether CARNs exist in the normal human prostate and if human prostate cancers originate from these CARNs. Dr. Shen's lab is now looking to investigate these issues.
This work was supported by grants from the National Institutes of Health, the Department of Defense Prostate Cancer Research Program, and the National Cancer Institute Mouse Models of Human Cancer Consortium.
The Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center and NewYork-Presbyterian Hospital encompasses pre-clinical and clinical research, treatment, prevention and education efforts in cancer. The Cancer Center was initially funded by the NCI in 1972 and became a National Cancer Institute (NCI)–designated comprehensive cancer center in 1979. The designation recognizes the Center's collaborative environment and expertise in harnessing translational research to bridge scientific discovery to clinical delivery, with the ultimate goal of successfully introducing novel diagnostic, therapeutic and preventive approaches to cancer. For more information, visit www.hiccc.columbia.edu.
Columbia University Medical Center provides international leadership in basic, pre-clinical and clinical research, in medical and health sciences education, and in patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Established in 1767, Columbia's College of Physicians and Surgeons was the first institution in the country to grant the M.D. degree and is now among the most selective medical schools in the country. Columbia University Medical Center is home to the most comprehensive medical research enterprise in New York City and state and one of the largest in the United States. Columbia University Medical Center is affiliated with NewYork-Presbyterian Hospital, the nation's largest not-for-profit hospital provider. For more information, please visit www.cumc.columbia.edu.
NewYork-Presbyterian Hospital, based in New York City, is the nation's largest not-for-profit, non-sectarian hospital, with 2,242 beds. The Hospital has nearly 2 million inpatient and outpatient visits in a year, including more than 230,000 visits to its emergency departments — more than any other area hospital. NewYork-Presbyterian provides state-of-the-art inpatient, ambulatory and preventive care in all areas of medicine at five major centers: NewYork-Presbyterian Hospital/Weill Cornell Medical Center, NewYork-Presbyterian Hospital/Columbia University Medical Center, NewYork-Presbyterian Morgan Stanley Children's Hospital, NewYork-Presbyterian Hospital/The Allen Pavilion and NewYork-Presbyterian Hospital/Westchester Division. One of the largest and most comprehensive health care institutions in the world, the Hospital is committed to excellence in patient care, research, education and community service. NewYork-Presbyterian is the #1 hospital in the New York metropolitan area and is consistently ranked among the best academic medical institutions in the nation, according to U.S.News & World Report. The Hospital has academic affiliations with two of the nation's leading medical colleges: Weill Cornell Medical College and Columbia University College of Physicians and Surgeons. For more information, visit www.nyp.org.
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