Fig. 1.

Structure and 3D model of mammary gland. (A) Luminal epithelial cells (LEP) forming the acinus are regulated by homotypic interactions with neighboring luminal cells, by heterotypic interactions with myoepithelial cells (MEP), and by interactions with the BM. The bi-layered structure is surrounded by a complex BM and a stroma comprised of stromal ECM, fibroblasts, and adipocytes, as well as nerves, blood, and lymphatic vessels (not depicted). This structure is disrupted in tumors. Additionally, myoepithelial cells surrounding the tumor have altered function [105,130]. (B) (left) In the 3D model of the normal mammary gland acinus, human or mouse mammary epithelial cells cultured in or on laminin-1-rich, malleable BM will form spherical structures with a central lumen. Addition of lactogenic hormones to mouse cells leads to the synthesis and vectorial secretion of milk proteins into the lumen (milk production by non-malignant human epithelial cells has not yet been achieved). Luminal epithelial cells fail to organize into an acinus when cultured in 3D collagen gels unless they receive signals from myoepithelial cells, which synthesize the laminin components of BM. (right) Oncogenic insults prevent tumorigenic epithelial cells from forming the acinus; these tumorigenic structures can be functionally reverted by restoring normal signaling pathways [52]. (B) modified from [131]. Red, BM; blue, MEPs; white/grey, LEPs; green, sialomucin.