Models of breast morphogenesis based on localization of stem cells in the developing mammary lobule.
Bottom Line: However, the identity of these cells is a subject of controversy and their localization in the breast epithelium is not known.In this study, we utilized a novel approach to analyze the morphogenesis of mammary lobules, by combining one-dimensional theoretical models and computer-generated 3D fractals.An increased representation of stem cells was found in smaller, less developed lobules compared to larger, more mature lobules, with marked differences in the gland of iparous versus parous women and that of BRCA1/2 mutation carriers versus non-carriers.
Affiliation: Research Oncology, King's College London School of Medicine, London SE1 9RT, UK. Electronic address: email@example.com.Show MeSH
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Mentions: To better define the localization of ALDH1A1+ cells within the 3D structure of lobules, we compared virtual sections through fractal trees with breast tissue sections (Figure 5A). ALDH1A1+ cells appeared to be present at branching points and ends of ductules, in agreement with the model shown in Figure 1B (model A1B2C1). This is consistent with observations in the mouse mammary epithelium, where stem cells are positioned at the growing ends of ducts, in the so-called terminal end buds, which are also the nodes of subsequent branching (Kenney et al., 2001). Furthermore, evidence from a number of studies (Mani et al., 2008; Scheel et al., 2011) shows that stem cells from the normal mammary epithelium can undergo epithelial to mesenchymal transition, which enables them to migrate and invade in the surrounding matrix. All these observations are also consistent with a distal location of stem cells at the growing ends of ductules, rather than proximally, at the base of the lobule. However, lobular development occurs through simultaneous proliferation in the entire structure; therefore, lobular or ductal stem cells may be seen in a proximal position, at branching points, and at the distal ends of ductules (Ewald et al., 2008; Villadsen et al., 2007).
Affiliation: Research Oncology, King's College London School of Medicine, London SE1 9RT, UK. Electronic address: firstname.lastname@example.org.