BME PhD Defense Seminar: Ryan Burke

The Role of Breast Tumor-Associated Macrophages in Collagen Microstructure Regulation as Visualized by Second Harmonic Generation

Supervised by Dr. Edward Brown

Abstract:

Studies in many tumor types have elucidated the extreme importance of the extracellular matrix (ECM) in tumor growth and progression. Despite a wealth of research into this area of tumor biology, challenges in identifying targetable signaling pathways by which tumors remodel their ECM to benefit their survival at the expense of the host remain. These challenges include the presence of multiple signaling pathways and redundancies, the ability of tumors to shift which pathways dominate in response to external manipulations, and the general lack of knowledge of these processes in vivo. To this end, second harmonic generation (SHG) imaging has been noted by several groups to be of use in visualizing the dynamic processes that result in ECM remodeling. Specifically, studies show that metastasizing tumor cells preferentially travel along SHG-producing fibers in escaping the primary tumor location, and that a region of SHG-producing collagen matrix is aligned normal to the tumor-host interface associated with these escaping cells, providing a direct physical path into peripheral vasculature. Therefore, we conjecture that a method of interference with the creation and maintenance of these specific fibers may be of interest in the development of pharmaceutical mechanisms against tumors.