Mar. 15, 2002 An international collaboration of scientists has successfully established a cell line that appears to function like adult human mammary stem cells. The report appears in the March 15th issue of the research journal Genes & Development.
Whereas embryonic stem cells are the building blocks for all of the cell types in the body, adult stem cells are a more specialized type of progenitor cell. Adult stem cells are found in specific tissues and have the ability to regenerate themselves, as well as differentiate into all of the cell types found in that tissue.
Dr. Ole William Petersen, graduate student Thorarinn Gudjonsson and colleagues at the University of Copenhagen in Denmark, along with Dr. Mina Bissell at the Lawrence Berkeley National Laboratory of the University of California, set out to generate a human breast stem cell line, knowing it would be an invaluable research tool.
Dr. Petersen and colleagues began their search for the breast stem cell in the luminal epithelial cell lineage within the terminal duct lobular unit (TDLU) of the breast, as most human mammary lesions originate there. The TDLU is a branching mammary structure that has luminal epithelial cells on the inside and myoepithelial cells on the outside. Working with tissue obtained from human patients undergoing cosmetic breast reduction surgery, Dr. Petersen and colleagues isolated a luminal epithelial cell population referred to as MUC-/ESA+ for the cell-type specific markers that were used to identify it.
After establishing a MUC-/ESA+ cell line, the researchers were able to show that these cells can give rise to both luminal epithelial cells and myoepithelial cells. The researchers also showed that a single MUC-/ESA+ cell is capable of generating a TDLU-like structure in culture, as is the cell line when implanted into immunocompromised mice.
Of particular interest to the researchers was the finding that these cells also express the keratin K19 protein, a characteristic shared with a subpopulation of luminal epithelial cells in the normal breast.
This work suggests that the long sought-after human breast stem cell exist within this population of the luminal epithelial cell lineage, a determination that may ultimately afford insight into the molecular mechanisms underlying malignant transformation and progression.
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