Human mammary luminal epithelial cells contain progenitors to myoepithelial cells

The origin of the epithelial and myoepithelial cells in the human breast ha s not been delineated. In this study we have addressed whether luminal epit helial cells and myoepithelial cells are vertically connected, i.e., whethe r one is the precursor for the other. We used a primary culture assay allow ing preservation of basic phenotypic traits of luminal epithelial and myoep ithelial cells in culture. The two cell types were then separated immunomag netically using antibodies directed against lineage-specific cell surface a ntigens into at best 100% purity. The cellular identity was ascertained by cytochemistry, immunoblotting, and 2-D gel electrophoresis. Luminal epithel ial cells were identified by strong expression of cytokeratins 18 and 19 wh ile myoepithelial cells were recognized by expression of vimentin and alpha -smooth muscle actin. We used a previously devised culture medium (CDM4) th at allows vigorous expansion of proliferative myoepithelial cells and also devised a medium (CDM6) that allowed sufficient expansion of differentiated luminal epithelial cells based on addition of hepatocyte growth factor/sca tter factor. The two different culture media supported each lineage for at least five passages without signs of interconversion. We used parallel cult ures where we switched culture media, thus testing the ability of each line age to convert to the other. Whereas the myoepithelial lineage showed no si gns of interconversion, a subset of luminal epithelial cells, gradually, bu t distinctly, converted to myoepithelial cells. We propose that in the matu re human breast, it is the luminal epithelial cell compartment that gives r ise to myoepithelial cells rather than the other way around. (C) 1999 Acade mic Press.