Deciphering the mammary epithelial cell hierarchy


Year:

Session type:

John Stingl
CRUK Cambridge Research Institute, Cambridge, United Kingdom

Abstract

The characterization of the cells that make up the mammary epithelium is essential for understanding the origins and the clinical presentation of breast tumours. To identify the cells that constitute this hierarchy, we used fluorescence-activated cell sorting (FACS) in combination with in vitro colony forming cell (CFC) assays and in vivo transplantation assays to examine the growth and differentiation properties of phenotypically distinct subsets of mammary epithelial cells. Our results indicate that in the mouse, mammary stem cells reside within the basal cell compartment and have a CD45-Ter119-CD31-(Lin-) EpCAMmedCD49fhigh phenotype, whereas the transit amplifying cells appear to reside within the luminal cell compartment since they have a Lin-EpCAMhigh phenotype. Further analysis of the luminal cell compartment  of the virgin mammary epithelium reveals that this population can be further resolved into 3 phenotypically distinct subsets of cells based on the differential expression of Sca1 and CD49b. Two of these subsets of cells are progenitors, one of which has a CD49b+ Sca1+ phenotype and expresses the estrogen receptor (ER) and the other has a CD49b+Sca1- phenotype and is ER- and has a basal-like breast cancer gene expression signature. The third and largest subset of cells is a population of ER+ cells that lacks clonogenic activity and have a CD49b-Sca1+ phenotype. Studies with human mammary epithelial cells reveals a similar hierarchical structure with mammary stem cells having a basal EpCAMlowCD49fhigh phenotype and a large population of progenitor cells that residing within the luminal cell compartment. These studies will provide a cellular framework for understanding the origins of breast tumours.