Figure 1

Alterations of the microenvironment from normal duct to in situ transition. (A) Schematic (transverse) view of a normal breast duct composed of a layer of luminal epithelial cells encircled by myoepithelial cells (green) and surrounded by a continuous basement membrane. Stroma containing fibroblasts, immune cells, and vasculature surrounded by the extracellular matrix maintains the normal tissue structure. (B) Longitudinal view of the normal duct and in situ carcinoma. In ductal carcinoma in situ (DCIS), epigenetically and phenotypically altered myoepithelial cells (shown as brown cells) are surrounded by a still largely continuous basement membrane. Altered myoepithelial cells in DCIS are unable to aid polarization and organize the structure of the normal duct. At the same time in the stroma, the numbers of fibroblasts and infiltrated leukocytes are increased and angiogenesis is enhanced. Cancer-associated fibroblasts (shown as yellow-green fibroblasts) and infiltrated leukocytes elevate secretion of growth factors, cytokines, chemokines, and matrix metalloproteinases (MMPs) to promote tumor progression. Potential cross-talk between cell-cell and cell-matrix interactions are aberrantly regulated by both autocrine and paracrine networks of proteolytic enzymes, cytokines, and chemokines (red arrows; not all possible interactions are indicated). Interactions between stromal and cancer cells may interact with each other via paracrine signaling rather than direct cell-cell contact.