title: Common adult stem cells in the human breast give rise to glandular and myoepithelial cell lineages: a new cell biological concept.
abstract: Breast biology and pathology are currently shaped by the two-cell concept that recognizes only glandular and myoepithelial cells. In the present study, we have visualized a previously unidentified cell population within the epithelial compartment of the breast, which displays the phenotypic characteristics of a committed stem cell. Immunofluorescence double labeling with digital image processing and Western blotting were applied to normal breast tissue as well as to noninvasive and invasive breast cancers using antibodies to basal cytokeratin 5 (Ck5), glandular cytokeratins 8/18 (Ck8/18/19), and smooth muscle alpha-actin (SMA) as markers for myoepithelial cells (SMA). A distinct population of cells was identified that expressed Ck5 in the absence of Ck8/18/19 or SMA. These cells differentiate toward glandular epithelial or myoepithelial Ck5-negative end cells passing through either Ck5/Ck8/18/19 or Ck5/SMA-positive intermediates. Our experiments clearly demonstrate a precursor or committed stem cell function of the Ck5-positive cell that is responsible for regeneration of the human adult breast epithelium. However, the observation that the vast majority of breast cancers display the glandular epithelial immunophenotype strongly suggests that the neoplastic cells derive from a late stage of the glandular epithelial differentiation pathway. The significance of this new cell biological model is that it might serve as a tool to unravel the regulatory mechanisms that govern regeneration and abnormal proliferation of breast epithelium at the cellular level.
authors.affiliation: Institute of Pathology, University of Münster, Münster, Germany. boeckew@uni-muenster.de
authors.forename: Werner
authors.initials: W
authors.lastname: Böcker
authors.forename: Roland
authors.initials: R
authors.lastname: Moll
authors.forename: Christopher
authors.initials: C
authors.lastname: Poremba
authors.forename: Roland
authors.initials: R
authors.lastname: Holland
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Van Diest
authors.forename: Peter
authors.initials: P
authors.lastname: Dervan
authors.forename: Horst
authors.initials: H
authors.lastname: Bürger
authors.forename: Daniel
authors.initials: D
authors.lastname: Wai
authors.forename: Raihanatou
authors.initials: R
authors.lastname: Ina Diallo
authors.forename: Burkhard
authors.initials: B
authors.lastname: Brandt
authors.forename: Hermann
authors.initials: H
authors.lastname: Herbst
authors.forename: Ansgar
authors.initials: A
authors.lastname: Schmidt
authors.forename: Markus M
authors.initials: MM
authors.lastname: Lerch
authors.forename: Igor B
authors.initials: IB
authors.lastname: Buchwallow
mesh_terms: D000199:Actins / Q000032:analysis; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western; D001940:Breast / Q000378:metabolism / Q000473:pathology*; D002278:Carcinoma in Situ / Q000378:metabolism / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000378:metabolism / Q000473:pathology; D018275:Carcinoma, Lobular / Q000378:metabolism / Q000473:pathology; D019070:Cell Lineage; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007633:Keratins / Q000032:analysis; D007774:Lactation / Q000378:metabolism; D008875:Middle Aged; D009130:Muscle, Smooth / Q000378:metabolism / Q000473:pathology; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*
chemical_list: D000199:Actins; D015415:Biomarkers; D007633:Keratins