Microenvironmental control of the breast cancer cell cycle.

The mammary gland is one of the best-studied examples of an organ whose structure and function are influenced by reciprocal signaling and communication between cells and their microenvironment. The mammary epithelial cell (MEC) microenvironment includes stromal cells and extracellular matrix (ECM). Abundant evidence shows that the ECM and growth factors co-operate to regulate cell cycle progression, and that the ECM is altered in breast tumors. In particular, mammographically dense breast tissue is a significant risk factor for developing breast carcinomas. Dense breast tissue is associated with increased stromal collagen and epithelial cell content. In this article, we overview recent studies addressing the effects of ECM composition on the breast cancer cell cycle. Although the normal breast ECM keeps the MEC cycle in check, the ECM remodeling associated with breast cancer positively regulates the MEC cycle. ECM effects on the downstream biochemical and mechanosignaling pathways in both normal and tumorigenic MECs will be reviewed.