Interstitial Flow in the Tumor Microenvironment: Contributions to Cancer Invasion and Progression

Date(s) - 03/18/2013
4:00 pm - 5:15 pm

Dr. Jennifer Munson, Post Doctoral Fellow, Swiss Federal Institute of Technology, Lausanne, Switzerland

Cancer invasion and metastasis are major obstacles to successful therapeutic response. There are many contributing factors to the progression of cancer towards metastasis, including interactions with the surrounding microenvironment. Biophysical factors such as interstitial flow, mediated by increased drainage from the tumor, and matrix stiffening, mediated by activated fibroblasts, yield increased invasion of cancer cells and metastasis. In this talk, I will present data showing the role of interstitial flow in brain cancer invasion. I will provide evidence for a chemokine (CXCL12)-mediated mechanism, involving both increased cell motility and autologous chemotaxis, using in vitro 3D models of the tumor microenvironment. In order to understand the role of interstitial flow in vivo, I will present data involving manipulation of lymphangiogenesis in breast and skin cancer to alter drainage. Using these models, I will show support for a hypothesis that increased lymphangiogenesis is tightly linked to fibroblast-mediated stromal stiffening in the tumor and draining lymph node which is largely mediated by the growth factor TGFβ. I will discuss the implications of this research and generally interstitial flow and its effects on the stroma in cell-cell communication and immune response.