Journal
INTERNATIONAL JOURNAL OF CANCER
Volume 135, Issue 10, Pages 2294-2304Publisher
WILEY
DOI: 10.1002/ijc.28726
Keywords
protease activated receptors; microenvironment; macrophage; chemoresistance
Categories
Funding
- Top Institute Pharma [T1-215]
- Dutch Cancer Society [AMC 2009-4324]
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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.
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