Myoepithelial cells: their origin and function in breast morphogenesis and neoplasia

Abstract

The human breast epithelium is a branching ductal system composed of an inner layer of polarized luminal epithelial cells and an outer layer of myoepithelial cells that terminate in distally located terminal duct lobular units (TDLUs). While the luminal epithelial cell has received the most attention as the functionally active milk-producing cell and as the most likely target cell for carcinogenesis, attention on myoepithelial cells has begun to evolve with the recognition that these cells play an active part in branching morphogenesis and tumor suppression. A major question that has been the subject of investigation pertains to how the luminal epithelial and myoepithelial lineages are related and precisely how they arise from a common putative stem cell population within the breast. Equally important is the question of how heterotypic signaling occurs between luminal epithelial and surrounding myoepithelial cells in normal breast morphogenesis and neoplasia. In this review we discuss data from our laboratories and from others regarding the cellular origin of human myoepithelial cells, their function in maintaining tissue polarity in the normal breast, and their role during neoplasia.

Fig. 1

Suprabasal epithelial cell lines make an elaborate TDLU-like structure in laminin-rich extracellular matrix (lrECM). Suprabasal epithelial cells embedded as single cells into lrECM form elaborate structures reminiscent of TDLU in vivo. Bar, 50 μm. Upper left, schematic drawing of TDLU showing luminal epithelial cells (red) and surrounded by myoepithelial cells (yellow) and basement membrane (black line). (Courtesy Gudjonsson et al. (4)).

Fig. 2

Reversal of inside-out acini by addition of myoepithelial cells. (A) Luminal cells make inside-out acini in collagen. Luminal epithelial cells were double-stained for MUC1 (red) and ESA (green). (B) In the presence of myoepithelial the acinar polarity is rescued as evidenced by apical expression of MUC1 (red) and ESA (green). Bar, 25 μm. (Courtesy Gudjonsson et al. (9)).

Fig. 3

Reduced staining of laminin-1 in human breast cancer. Cryostat sections of TDLU (a), a ductal carcinoma in situ (b), and four different infiltrating ductal breast carcinomas (IDC) (c–f) stained with immunoperoxidase for laminin-1 and counterstained with hematoxylin. Note the strong staining of laminin-1 in basement membrane of TDLU separating the stromal (S) and epithelial (E) compartments in (a). In carcinomas, laminin-1 staining is localized to the stromal (S)-cancer epithelial (C) interface, but is discontinuous and less pronounced. Bar, 25 μm. (Courtesy Gudjonsson et al. (9)).