Fig. 1.

Computational domain, cell phenotype hierarchy, and signaling pathways. A) The mature mammary gland duct is composed of an outer myoepithelial layer and an inner luminal layer, both surrounding the duct cavity. At time t = 0, we initiate a number of tumor initiating cells (TICs) within the luminal population, initiating the onset of DCIS. B) Cross-sectional schematic of a duct section shows DCIS phenotypic hierarchy and signaling pathways. Cell signaling is as shown, with estrogen from the bloodstream signaling to the ER+ population and upregulating proliferation. These cells are stimulated to produce AREG, which leaves through the duct boundary and into the stroma, upregulating production of FGF, which reenters the duct, binding to and upregulating proliferation in the ER− phenotype; for simplicity, not all agent types are shown. C) Legend for agent color coding and signaling pathways as shown in A and B. Note that we combine all cell types into necrotic and lysed/calcified, as phenotype is no longer pertinent in these dying/dead agents. Further, all residual material from the lysis process from each individual agent (cytoplasmic contents, calcified remains, etc.) are summed together and represented by a single agent (light green).