Biomedical Engineering Reference
In-Depth Information
In the developing mammary gland, three cell lineages have been described:
myoepithelial cells that form a basal cell layer, ductal epithelial cells, and milk-
producing alveolar cells (Dean et al., 2005; Deugnier et al., 2002). Although
transplantation studies in mice have demonstrated that most mammary cells
have a limited capacity for self-renewal, clonal populations that can recapitu-
late the entire functional repertoire of the gland have been identified (Smith,
2006; Smith and Boulanger, 2002). In an elegant study, human mammary
epithelial cells derived from reduction mammoplasties were used to generate
non-adherent spheroids (designated mammospheres) in cell culture and demon-
strate the presence of three mammary cell lineages. More importantly, the cells
in the mammospheres were clonally derived, providing evidence for a single
pluripotent stem cell (Dontu et al., 2003). These same approaches are being used
to isolate and characterize breast cancer stem cells (Xiao et al., 2008).
3 Breast Embryology
From the fifth to seventh week of pregnancy, a human fetus develops a mam-
mary ridge, which rises from the axilla to the inguinal region (Ameryckx et al.,
2005). By the sixth gestational week, this ridge depresses into the pectoral
region, forming primary breast buds (Moore et al., 1993). At birth the main
lactiferous ducts are present as well as the nipples and areola (Black et al., 1998).
After puberty, estrogen secretion at each menstrual cycle stimulates prolif-
eration and active growth of breast tissue (Clarke, 2003). Breast development
proceeds with growth of the ductile system and the formation of ductile buds
(Black et al., 1998). Surrounding fat pads also develop, giving the breast size
and shape unrelated to functional capacity (Riordan, 2005).
Estrogen is a potent mammary mitogen that has numerous salutary systemic
effects (Ho and Liao, 2002): estradiol, the most active form, decreases risk of
coronary artery disease in women between puberty and menopause, a decrease
in risk that is not observed in postmenopausal women (Rossouw, 2000). Experi-
mental studies have showed exogenous estrogen can preserve endothelium
critical for coronary artery dilation, reduce infarct size, decrease the occurrence
of ventricular arrhythmias, and protect against ischemia-reperfusion injury
(McCullough et al., 2001; Zhai et al., 2000a,b). Estradiol is also a neuroprotec-
tive and neurotrophic factor: it has a positive influence on memory and cogni-
tion and may decrease the risk of Alzheimer disease and stroke (Brinton, 2001;
Norbury et al., 2003). Finally, estrogen receptor immunostaining has enabled
observation of hormonal effects on osteoblasts on the medullary bone surface.
Such studies show that estrogen receptors are present in osteogenic cells and
suggest that estrogen directly acts on medullary bone osteogenesis (Jilka, 1998).
In spite of all these positive activities, exogenous estrogens bring a risk of
neoplasia in responsive tissues, probably because of their potent activity as
mitogens (Auersperg et al., 2001; Jordan and Morrow, 1999; McLachlan, 2001;
