Protease activated receptor (PAR)-1 expression in tumor cells is associated with disease progression and overall survival in a variety of cancers of epithelial origin; however, the importance of PAR-1 in the tumor microenvironment remains unexplored. Utilizing an orthotopic pancreatic cancer model in which tumor cells are PAR-1 positive whereas stromal cells are PAR-1 negative, we show that PAR-1 expression in the microenvironment drives progression and induces chemoresistance of pancreatic cancer. PAR-1 enhances monocyte recruitment into the tumor microenvironment by regulating monocyte migration and fibroblast dependent chemokine production thereby inducing chemoresistance. Overall, our data identify a novel role of PAR-1 in the pancreatic tumor microenvironment and suggest that PAR-1 may be an attractive target to reduce drug resistance in pancreatic cancer.
CITATION STYLE
Queiroz, K. C. S., Shi, K., Duitman, J. W., Aberson, H. L., Wilmink, J. W., Van Noesel, C. J. M., … Spek, C. A. (2014). Protease-activated receptor-1 drives pancreatic cancer progression and chemoresistance. International Journal of Cancer, 135(10), 2294–2304. https://doi.org/10.1002/ijc.28726
Mendeley helps you to discover research relevant for your work.