Speaker: Ian Schneider, Iowa State University Department of Chemical and Biological Engineering

Abstract: The tumor microenvironment is complex, consisting of many cell types that shape its structural and mechanical properties through the assembly of collagen fiber networks. Most normal tissue contains randomly oriented collagen fibers that form a relatively soft environment. As the tumor progresses, collagen is aligned perpendicularly to the tumor margin and is crosslinked to form a stiff extracellular matrix. Both structural and mechanical properties can modulate cell migration characteristics like speed and persistence. Furthermore, aligned fibers and gradients in stiffness can direct cell migration towards particular targets in processes called contact guidance and durotaxis, respectively. Consequently, it is not surprising that high invasion and poor prognosis in both breast and pancreatic cancers correlate with aligned, stiff collagen. However, several questions remain. Do all cells in the tumor microenvironment respond to these directional cues to the same extent? What cytoskeletal pathways allow this sensing? How do other components of the tumor microenvironment modulate these migration responses? Along with migration, cells can remodel the collagen fiber networks through degradation and force transmission, dramatically changing structure and mechanics. How do cancer and normal cells cooperate during this process? Which molecular regulators can be used to alter the extracellular matrix from a tumor-promoting (stiff, aligned) to normal (soft, disorganized) extracellular matrix? In this talk I will present some engineering approaches that we use to control structural and mechanical properties ex vivo in an attempt to mimic the tumor microenvironment. In addition, I will outline some insight into how cells migrate through or remodel the extracellular matrix in the tumor microenvironment. Understanding these cell responses will allow us to suggest approaches for either blocking directed migration leading to invasion or reprogramming the extracellular matrix from tumor-promoting to tumor-inhibiting. 

Host: Steve Howell

Please join us for refreshments before the seminar outside Room 1414 in the Molecular Biology Building at 3:45 p.m.