Protease-activated receptor-1 drives pancreatic cancer progression and chemoresistance
Protease-activated receptor-1 drives pancreatic cancer progression and chemoresistance
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DOI：
10.1002/ijc.28726
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发表时间：
2014-11-15
影响因子：
6.4
通讯作者：
Spek, C. Arnold
中科院分区：
文献类型：
--
作者：
Queiroz, Karla C. S.;Shi, Kun;Spek, C. Arnold
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.
