Saam Shahrokhi Rose Hills
Developing a Mechanical Model for Self-Organization in the Mammary Duct
It is estimated that about 300,000 women will be diagnosed with breast cancer in 2016, making it cancers most common form. About twenty percent of these cases are classified as ductal carcinoma in situ (DCIS), meaning that within the milk duct (ductal) of the mammary gland, cancerous epithelial tissue (carcinoma) has formed, and it is still localized to where it originally developed (in situ). At this stage, ductal carcinoma is not lethal, and a simple lumpectomy can often be performed to remove malignant tissue. However, if the cancer cells proliferate to a certain extent before any treatment is performed, they breakout of their local milk ducts, begin invading other parts of the breast, and eventually get to other parts of the body. The stage of ductal carcinoma characterized by this spread is simply called invasive/infiltrating ductal carcinoma (IDC). The remaining eighty percent of cancer case diagnoses conclude a patient has this lethal form of breast cancer. Understanding how cancerous cells disrupt the healthy tissue structure of the milk duct, and finding out how the milk duct maintains a healthy tissue structure in general is essential to restraining breast cancer to DCIS.
A healthy milk duct has a cylindrical inner cavity called a lumen, which is lined by a two-layer tissue architecture. Luminal epithelial cells (LEPs) make up the inside layer of this lining, while myoepithelial cells (MEPs) constitute the lining’s outside layer. How exactly MEPs and LEPs organize themselves to form this architecture is of interest. My lab recently demonstrated that tissue self-organization is likely to be mechanically driven. The epithelial cells are in a dynamic mechanical microenvironment, where they interact with each other, the extracellular matrix, and have cytoskeletons that are contractile. Each of these interactions contributes to an interfacial tension and energy. From a mechanical perspective, the minimization of the overall interfacial energy of the tissue guides self-organization. Only on a qualitative basis do we understand what molecules contribute to adhesive forces and cellular tensions during tissue formation. My project involves quantifying the energy contributions from each of these factors and developing a mechanical model that explains how self-organization in MEPs and LEPs occurs and how it is maintained. The insight gained from this research can extend to functional tissue engineering, understanding the morphogenesis of other organs such as the prostate, and developing better treatments or diagnostic methods for breast cancer.