Human Mammary Luminal Epithelial Cells Contain Progenitors to Myoepithelial Cells

Abstract

The origin of the epithelial and myoepithelial cells in the human breast has not been delineated. In this study we have addressed whether luminal epithelial cells and myoepithelial cells are vertically connected, i.e., whether one is the precursor for the other. We used a primary culture assay allowing preservation of basic phenotypic traits of luminal epithelial and myoepithelial cells in culture. The two cell types were then separated immunomagnetically using antibodies directed against lineage-specific cell surface antigens into at best 100% purity. The cellular identity was ascertained by cytochemistry, immunoblotting, and 2-D gel electrophoresis. Luminal epithelial cells were identified by strong expression of cytokeratins 18 and 19 while myoepithelial cells were recognized by expression of vimentin and alpha-smooth muscle actin. We used a previously devised culture medium (CDM4) that 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/scatter factor. The two different culture media supported each lineage for at least five passages without signs of interconversion. We used parallel cultures where we switched culture media, thus testing the ability of each lineage to convert to the other. Whereas the myoepithelial lineage showed no signs of interconversion, a subset of luminal epithelial cells, gradually, but distinctly, converted to myoepithelial cells. We propose that in the mature human breast, it is the luminal epithelial cell compartment that gives rise to myoepithelial cells rather than the other way around.

Diagnostic utility of p75 neurotrophin receptor (p75NTR) as a marker of breast myoepithelial cells

“…Similarly, other authors have reported decreased CD10 and SMA expression in continuously passaged purified human breast myoepithelial cells. 20 We have found that the myoepithelial component of adenomyoepitheliomas often does not express CD10 and/or myosin, while SMA expression often decreases. 18 All of these facts suggest that a panel containing complementary myoepithelial markers should be used when an evaluation of myoepithelial cells or tumor phenotype is required.…”

“…p75 NTR has been previously detected in the nerves 13,14,[11][12][13][14][15][16][17][18][19][20][21][22][23] and vessels. 13,14 Although we did not observe significant p75 NTR expression in the fibroblast in normal breast stroma and in the stroma around the carcinoma, we found strong p75 NTR expression in the fibroblasts of the expanding intralobular stroma (fibroadenomatoid change).…”

Myoepithelial Cells: Their Origin and Function in Breast Morphogenesis and Neoplasia

“…The data indicating that myoepithelial cells arise from progenitor cells within the luminal epithelial compartment (3,40) and that (an) extrinsic factor(s) may trigger a subset of luminal cells to convert to myoepithelial cells could partially explain why the majority of breast carcinomas express a luminal phenotype. If the extrinsic signal(s) is not present or the cells lose their ability to respond to the microenvironment appropriately (80), the stem/progenitor cells continue to expand along the luminal epithelial lineage, thus avoiding, or partially bypassing, the myoepithelial route, as postulated previously by Rudland on the basis of the behavior of rat cell lines (81,82).…”

“…However, the myoepithelial cells will reexpress the α-sm actin upon addition of serum at confluence (3). Using the purified cell populations, it was possible to address which cell type gave rise to the other by switching the culture medium.…”

“…This process gives rise to the airways of the lungs, the urine-collecting ducts, the prostate and salivary glands as well as the functional unit of the breast (2). There is ample evidence from both mice and humans that the two different epithelial cells that make up the TDLU, luminal epithelial and myoepithelial cells, are derived from common ancestors, namely the breast epithelial precursor cells positioned within the luminal epithelial compartment (3,4).…”