Understanding Collagen Organization in Breast Tumors to Predict and Prevent Metastasis

The ordering of collagen fibers within a tumor has significant influence on tumor metastasis in murine breast tumor models, tumor cells move towards blood vessels along fibers that are visible via second harmonic generation SHG, and SHG is exquisitely sensitive to molecular ordering. Tumor cells that are moving along SHG-producing i.e. ordered collagen fibers move significantly faster than those cells that are moving independently of SHG-producing fibers, and the extent of SHG-associated tumor cell motility is correlated with metastatic ability of the tumor model. Furthermore, the tumor-host interface of murine breast tumor models is characterized by radially oriented SHG-producing fibers associated with tumor cells invading the surrounding tissue. Consequently we believe that the process of establishing ordered fibers offers an exciting, and currently unexploited, therapeutic target. To take advantage of this, we must first learn the cellular players and molecular signals by which collagen ordering is induced. Therefore, in this application we propose to determine the key cells and signals which influence the ordering of collagen in breast tumors, determine if this ordering is predictive of metastasis, and develop new optical tools to study this ordering.