Self-Defense Mechanisms of Normal Breast Cells

Human mammary epithelial cells grown in a 3D matrix form polarized acini that closely resemble the cellular environment encountered in breast tissue. Consequently, acini are an excellent system for studying morphogenesis, and for modeling the role of cell-cell interactions in processes such as apoptosis, tumorigenesis and carcinogenesis. In this project, we studied the interaction of an aggressive mammary epithelial tumor cell line with the MCF-10A acini. We found that MCF-10A acini have the ability to induce apoptosis in tumor cells, whereas non-polarized MCF-10A cells those in monolayers rather than acini show no such mechanism. We also showed that tumor cell apoptosis induced by contact with MCF-10A acini is mediated by the extrinsic Fas death signaling pathway. We believe this is an example of tissue homeostasis, in which the normal mammary epithelial cells regulate the growth of aberrant epithelial cells. This model system can be used to study the ways in which tumor cells evade this early control mechanism enabling their uncontrolled growth and proliferation.