Figure 1. Modeling Tumor-Stroma Co-Evolution: Spontaneous Development of Tumor Subtypes and Stromal Subtypes in Human Breast Cancer.

Collaboration of both the epithelial and stromal compartments during tumor development contributes to the biological diversity in breast cancer and could be associated with various clinical parameters and patient outcomes, i.e. a basal like tumor developing in combination with stromal subtype 1 may be more aggressive or more resistant to treatment than the same basal like tumor developing simultaneously with stromal subtype 4. Conversely, the presence of a particular subtype of stroma might adversely affect growth of a particular tumor subtype, thereby predicting a better patient outcome. By examining the effects of stromal Pten signaling in several models of breast cancer in mice, we were able to show cooperation between Pten and both ErbB2 and c-myc, however not between Pten and Ras. Similar experiments are underway to examine the collaboration of p53 in stromal fibroblasts with various oncogenes in mammary epitheial cells. Using gene signatures from various cell types in these and other models currently being developed, we will have a powerful tool in predictive biomarkers for both human tumor and stromal samples.