Defects in Adult Stem Cells May Cause Breast Cancer
Scientists at Georgetown's Lombardi Comprehensive Cancer Center have found that the onset of breast cancer may be due to defects in somatic adult stem cell niches that exist long before tumors develop.
The research, published in the October 2005 issue of Tissue and Cell, is the first to examine the highly specialized microenvironment, termed the stem cell niche, which surrounds adult stem cells, and its role in breast cancer development. These niches are key regulators of stem cell activity in mammary tissue, and defects that develop in these groups of cells can give rise to breast cancer.
"This study helps us understand adult stem cells differently than we previously did. Particularly, when looking for the causes of breast cancer, we must take into account the stem cell as well as the environment that surrounds it," said Robert Dickson, Ph.D., co-author of the paper and co-director of the breast cancer program at the Lombardi Comprehensive Cancer Center.
The study used genetically engineered mice as models of ductal or lobular breast cancer that is caused by overproduction of certain proteins. These proteins (c-Myc and TGF-alpha) exist naturally in the body, but when produced in excess in mammary tissue cells, breast cancer can develop.
Gloria Chepko, Ph.D., a postdoctoral fellow and the paper's lead author, built on previous research results that demonstrated the existence of five different types of cells in normal breast tissue. Two of the cell types are stem cell-like and give rise to the other three. For the present study, she devised a method to identify all the cell types at low magnification, allowing more cells to be counted. This method revealed not only that each cell population has a different size in normal breast tissue, but also that the different cells are arranged in particular relationships to each other. The arrangements form repeating units called stem cell niches and provide nest-like microenvironments that house the adult stem cells and their immediate daughter cells.
In the mice that expressed excess amounts of either of the cancer-producing proteins, the size of the cell populations were significantly changed relative to each other. The order of the cell arrangements was disrupted in the stem cell niches of mice with breast cancer. These results provided the first evidence that each cell population may play a different role in the development of breast cancer and that the environment in which a cell grows can influence its chance of becoming malignant.
"The results also show how complicated cancer is as a disease. Eventhough it's not something that will be solved easily or quickly, our study reveals important information on the genesis of breast cancer in the body," said Chepko.
The study was funded in part by a grant from the National Institutes of Health and by a grant from the Department of Defense, both of which received funds from sales of the U.S. Postal Service breast cancer stamp. Co-authors include Rebecca Slack, M.S., Deborah Carbott, Sonya Khan and Lynley Steadman from Georgetown University.
The Lombardi Comprehensive Cancer Center, part of Georgetown University Medical Center and Georgetown University Hospital, seeks to improve the diagnosis, treatment and prevention of cancer through innovative basic and clinical research, patient care, community education and outreach, and the training of cancer specialists of the future. Lombardi is one of only 39 comprehensive cancer centers in the nation, as designated by the National Cancer Institute, and the only one in the Washington DC area. For more information, go to http://lombardi.georgetown.edu/