Dissection of a stem cell hierarchy in the human breast
Abstract:The human breast is a unique organ in that it undergoes most of its development after birth under the control of systemic hormones. The adult human breast undergoes impressive cycles of cell proliferation and apoptosis during pregnancy and with the menstrual cycle many times throughout the reproductive life of women. These highly dynamic changes are thought to rely on the presence of a mammary stem cell population. Recently, we have succeeded in defining a stem cell hierarchy as well as a stem cell zone located in ducts in the normal human mammary gland. In the present study we have utilized multiparameter cell sorting to enable us to isolate two hitherto uncharacterized progenitors present in the luminal compartment of the mammary gland. One population defines a lineage-restricted progenitor with the capacity of expressing endocrine receptors. The other compartment is enriched for cells with stem cell activity, including the ability to form TDLU-like structures in laminin-rich extracellular matrix. Further characterization of these populations included testing for the expression of markers for stem cell activity, lineage-differentiation, anti-apoptotic pathways as well as defining optimal culture conditions for propagating these cells in vitro. In conclusion, characterization of these cells may lead to identification of those long-term breast resident(s) that accumulate enough genetic hits for clonal expansion and tumor development, i.e. the cellular origin(s) of breast cancer.
Document Type: Abstract
Affiliations: 1: Institut for Cellulær og Molekylær Medicin, Kbh's Universitet, Blegdamsvej 3b, Bygning 18.4, 2200 Kbh N 2: Biologisk Institut, August Krogh Bygningen, 326, Kbh's Universitet, Universitetsparken 13, 2100 Kbh Ø, Denmark
Publication date: 2008-05-01