@article{097f5e2ca5db4e33beb1b02c2458f0d7,
title = "Stat3 and MMP7 Contribute to Pancreatic Ductal Adenocarcinoma Initiation and Progression",
abstract = "Chronic pancreatitis is a well-known risk factor for pancreatic ductal adenocarcinoma (PDA) development in humans, and inflammation promotes PDA initiation and progression in mouse models of the disease. However, the mechanistic link between inflammatory damage and PDA initiation is unclear. Using a Kras-driven mouse model of PDA, we establish that the inflammatory mediator Stat3 is a critical component of spontaneous and pancreatitis-accelerated PDA precursor formation and supports cell proliferation, metaplasia-associated inflammation, and MMP7 expression during neoplastic development. Furthermore, we show that Stat3 signaling enforces MMP7 expression in PDA cells and that MMP7 deletion limits tumor size and metastasis in mice. Finally, we demonstrate that serum MMP7 level in human patients with PDA correlated with metastatic disease and survival.",
author = "Akihisa Fukuda and Wang, {Sam C.} and Morris, {John P.} and Folias, {Alexandra E.} and Angela Liou and Kim, {Grace E.} and Shizuo Akira and Boucher, {Kenneth M.} and Firpo, {Matthew A.} and Mulvihill, {Sean J.} and Matthias Hebrok",
note = "Funding Information: We thank all of our colleagues who shared the indicated mouse lines as detailed in the Experimental Procedures section, Cecilia Austin for tissue processing and preparation, and all Hebrok lab members for helpful discussion. Imaging experiments were supported by the UCSF Diabetes and Endocrinology Research Center. Work in Hebrok Laboratory was supported by the Pancreatic Cancer Action Network and the NIH (CA112537). A.F. was supported by a postdoctoral Research Fellowship of the Japan Society for the Promotion of Science, the Klein Family Foundation, and the National Pancreas Foundation. S.C.W. was supported by the NIH under Ruth L. Kirschstein National Research Service Award F32 from the National Cancer Institute and the American College of Surgeons Resident Research Scholarship. Work at the University of Utah was supported by the NIH (R03 CA115225 to S.J.M. and P30CA042014 to the Huntsman Cancer Institute for core facilities), the Huntsman Cancer Institute Pancreas Cancer Research Program, and the Huntsman Cancer Foundation. The authors declare that no conflicts of interest exist. ",
year = "2011",
month = apr,
day = "12",
doi = "10.1016/j.ccr.2011.03.002",
language = "English",
volume = "19",
pages = "441--455",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "4",
}
