Interrogating consequences of interactions between breast carcinoma cells and tumor fibroblasts

While it is becoming increasingly apparent that interactions between carcinoma cells and tumor stroma are an essential part of tumor biology, our understanding of this crosstalk is far from complete. Using organotypic 3D culture models, we are interrogating mutual changes in transcriptome, metabolome, and phospho-proteome that result from the interaction between breast carcinoma cells and primary breast tumor-associated fibroblasts.

Myoepithelial cells and leukocytes in DCIS

The progression from in situ to invasive carcinoma is a key but poorly understood step of breast tumorigenesis, characterized by loss of the myepithelial cell layer and basement membrane. We hypothesize that the differentiation of bipotential mammary epithelial progenitors to myoepithelial cells is progressively inhibited by signals coming from tumor epithelial cells and stromal cells, such as leukocytes, leading to their eventual disappearance. Project objectives include:

• Defining normal myoepithelial cell differentiation and its abnormalities in DCIS

• Characterizing the role of immune cells in myoepithelial cell differentiation during breast carcinoma progression using in vivo and in vitro model systems and human breast tissue

The completion of this project will increase our understanding of the role of myoepithelial and immune cells in breast cancer, and may also provide new targets for breast cancer treatment via abnormally expressed paracrine signaling in the tumor microenvironment.