The Epithelial-Stromal Interaction as a Potential Target for Breast Cancer Treatment

Tumor behavior and outcome are believed to be modified by undifferentiated stromal fibroblasts that surround epithelial cells. An understanding of the biology of these fibroblasts could shed light on the mechanisms underlying tumor growth, invasion and progression, and may suggest new targets for therapy. In breast cancer, interactions between malignant breast epithelial cells and fibroblasts are responsible for estrogen biosynthesis. Preclinical studies showed that breast cancer epithelial cells secrete factors that enhance the expression and activity of the estrogen-synthesizing enzyme aromatase in undifferentiated adipose fibroblasts. Clinicopathological data showing an abundance of stroma cells in breast cancer, and the clinical finding that aromatase inhibitors are effective in breast cancer treatment indicate that stromal cells play a prominent role in the microenvironment of breast cancer tissue. The analysis of the stromal signature could provide information about the molecules involved in the epithelial-stromal interaction and reveal new potential treatment targets in distinct biological processes. This article focuses on breast cancer in terms of: 1) epithelial and stromal cell populations; 2) epithelial-stromal signaling and targeted therapies; and 3) stroma-related molecular signatures as a tool to identify potential candidate molecules for target therapy.