The tumor microenvironment (TME) is a complex combination of stromal cells and extracellular matrix. The cancer-associated fibroblast (CAF) plays an integral role in remodeling the TME and promoting tumor aggression. In this study, we present a 3D microfluidic model of the tumor stroma, which consists of a single straight micro-channel filled with CAF-embedded or acellular collagen gels. Using this platform, we can quantify both fiber alignment and hydraulic permeability within the collagen matrix. These results provide an enhanced understanding of the CAF's influence on the TME, and this knowledge is critical to the development of more effective cancer treatments. First, this study shows that genetic silencing of phosphatase and tensin homolog (PTEN) in CAFs causes a significant decrease in hydraulic permeability. Moreover, this change occurs without physical reorientation of the collagen fibers, thereby suggesting that PTEN deleted CAFs may be secreting molecules β hypothesized to be hyaluronan β into the TME to cause this observed effect. Using our microsystem as a drug screening platform, we also (1) identify the application of hyaluronidase and the inhibition of p-AKT as promising methods for mitigating the adverse effects of PTEN deletion and (2) show that GDC-0449 undesirably decreases the hydraulic permeability of the TME. Finally, we have also utilized our microsystems to measure the properties of various acellular ECM gel compositions and compared these results to our CAF data. Our findings suggest that HA supplementation to collagen gels does not have an equivalent effect on matrix architecture as CAF-secreted HA. Overall, this study demonstrates the utility of our microfluidic model for studying the TME and provides key insights for developing more effective cancer treatments.The College of EngineeringPelotonia Undergraduate Fellowship ProgramA one-year embargo was granted for this item.Academic Major: Biomedical Engineerin
