A visual-quantitative analysis of fibroblastic stromagenesis in breast cancer progression

One fundamental difference between normal and transformed cells is the way they interact with their immediate environment. Exploring this difference is crucial for understanding the pathobiology of cancer progression. Benign epithelial tumors are constrained by a surrounding stroma consisting, among other cells, of fibroblasts embedded within fibrillar three-dimensional matrices. However, at a critical point in tumor progression, tumor cells become altered and overcome the barrier, inducing changes in the stroma, which promote, rather than impede, tumor progression. Inherited or acquired genetic aberrations affecting mammary gland epithelia are usually blamed for promoting neoplasia in individuals at "high risk" for breast cancer. However, in addition to these epithelial aberrations certain individuals possess permissive breast stroma. The occurrence of this permissive stroma results in a predisposition for cancer initiation or progression. Here we review stromagenic stages, experimental 3D systems, and discuss digital imaging analyses suitable for uncovering the mechanisms behind fibroblastic breast stromagenesis.