Abstract 1494: The role of microenvironment in mammary epithelial cell plasticity

Abstract Understanding breast cancer heterogeneity is crucial for the development of targeted therapeutic interventions. One source of this intratumoral diversity comes from changes induced in epithelial cells by signals they receive from the stromal microenvironment. These changes include the epithelial-to-mesenchymal transition (EMT), a process of cellular plasticity by which epithelial cells disengage cell-cell and cell-extracellular matrix interactions, alter cytoskeletal structure, and implement a transcriptional program that facilitates the acquisition of aggressive traits, such as increased motility, invasiveness and resistance to apoptosis. Bissell lab has demonstrated that an extracellular protease, matrix metalloproteinase-3 (MMP3), is able to initiate the formation of mammary tumors in mice, as well as trigger EMT in mammary epithelial cells when activated. Furthermore, the observed EMT in MMP3-overexpressing cells was found to be dependent upon reactive oxygen species (ROS) production. However, it is not clear how this extracellular secreted protein functions with an epithelial cell to affect its intracellular events. To understand the mechanism by which MMP3 drives transformation of mammary cells, we asked which domain of MMP3 is required for ROS production or EMT in mammary epithelial cells, and we are investigating cell surface proteins that may be target of degradation or binding partner of MMP3 during tumorigenesis. This work will unravel new candidates for specific inhibition, providing attractive options for treatment of this and other diseases in which MMP3 plays a pathological role. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1494. doi:10.1158/1538-7445.AM2011-1494