Colony-forming cell assays that use luminal progenitor ce...

Colony-forming cell assays that use luminal progenitor cells isolated from normal adult human mammary glands show that luminal progenitor cells primarily form luminal epithelial colonies (Stingl et al. 2005, Raouf et al. 2008, Hilton et al. 2012). Different subtypes of luminal progenitor cells have been discovered by single cell omics methods, the best characterized being hormone receptor positive and hormone receptor negative, with the latter producing hormone receptor negative luminal epithelial cells (reviewed in Visvader and Stingl 2014).

EGFR ligands EGF and AREG stimulate differentiation of the luminal cell lineage (Pasic et al. 2011, Mukhopadhyay et al. 2013). Omission of EGF from the growth medium markedly reduces cloning efficiency of EPCAM+;EGFR- mammary luminal progenitor cells derived from MaSC-like cells of the normal adult human breast (Stingl et al. 2001).

While luminal progenitor cells express both EPCAM and ITGA6 (CD49f) proteins on their surface, mature luminal epithelial cells express EPCAM but are negative for ITGA6 (Lim et al. 2010, Prat et al. 2013, Prasad et al. 2019, Martin Carli et al. 2020). At the mRNA level, going from luminal progenitors to mature luminal epithelial cells, the level of EPCAM mRNA is similar, but the level of ITGA6 mRNA decreases (Prat et al. 2013). KRT18 mRNA level is higher in mature luminal epithelial cells than in luminal progenitors, while the mRNA level of KRT19 is similar between the two cell types (Prat et al. 2013). Level of KRT5 mRNA and protein decreases going from luminal progenitors to mature luminal epithelial cells, so that KRT5 protein is undetectable in the latter (Prat et al. 2013), while the level of KRT8 protein increases in mature luminal epithelial cells compared to luminal progenitors (Prat et al. 2013, Nguyen et al. 2018).