(466g) Using Physical Models of the Tumor Microenvironment to Identify Invasive Cancer Cells (INVITED SPEAKER)

The Dawson Cell Biophysics Lab uses a single cell biophysical approach to study tumor microenvironment interactions; research is focused on breast and ovarian cancer, which are leading causes of cancer-related death in women. The microenvironment in these tumors includes a multitude of cell types, matrix proteins, and growth factors that profoundly influence cancer cell behavior by providing both physical and chemical stimulation. This microenvironment, which is both dynamic and heterogeneous in nature, plays a critical role in cancer progression from the growth of the primary tumor to the development of metastatic and drug-resistant tumors. Our single cell biophysical approach, can be used to systematically investigate physical and paracrine interactions between cancer and stromal cells, and to identify specific conditions in the tumor that induce tumor-promoting behavior, along with strategies for inhibiting these conditions to treat cancer. This approach has helped us to identify rare populations of invasive and chemoresistant cancer cells, along with changes in the tumor microenvironment that contribute to their formation. In vitro studies of breast and ovarian cancer have primarily focused on adherent cells grown in 2D monolayers; however, 3D culture systems that more accurately mimic the in vivo tissue microenvironment are critical research tools in studying cancer. Our lab has developed 3D organoid culture models to study tumor growth, matrix invasion, and tumor drug response with spatial and temporal control in a single model of the tumor microenvironment. This research will increase our fundamental knowledge of cancer biology and provide critical information about how the 3D microenvironment influences tissue growth and development at all stages. Our long term goal is to use these in vitro systems to understand how heterogeneity develops in the tumor and contributes to the formation of invasive and drug-resistant outlier cell populations. My presentation will focus on lessons we’ve learned through quantitative biophysical analysis of cells in the tumor microenvironment. I will also discuss current research projects focused on investigating the role of stromal cell aging in cancer progression and mechanisms contributing to chemotherapy and radiation resistance through the formation of polyploidal giant cancer cells.