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Protease‐activated receptor‐1 drives pancreatic cancer progression and chemoresistance
Author(s) -
Queiroz Karla C.S.,
Shi Kun,
Duitman JanWillem,
Aberson Hella L.,
Wilmink Johanna W.,
Noesel Carel J.M.,
Richel Dick J.,
Spek C. Arnold
Publication year - 2014
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.28726
Subject(s) - pancreatic cancer , tumor microenvironment , stromal cell , cancer research , tumor progression , chemokine receptor , cancer , chemokine , biology , fibroblast activation protein, alpha , pancreatic tumor , receptor , medicine , tumor cells
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.