| Stat3 and MMP7 contribute to pancreatic ductal adenocarcinoma initiation and progression. | |
| | |
MedLine Citation:
|
PMID: 21481787 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
Akihisa Fukuda; Sam C Wang; John P Morris; Alexandra E Folias; Angela Liou; Grace E Kim; Shizuo Akira; Kenneth M Boucher; Matthew A Firpo; Sean J Mulvihill; Matthias Hebrok |
Related Documents
:
|
7879707 - Histamine increases anti-cd3 induced il-5 production of th2-type t cells via histamine ... 21318047 - A nonsecosteroidal vitamin d receptor modulator ameliorates experimental autoimmune enc... 10951887 - Immunomodulation and allergy. 16364157 - Cytokine and ig-production by cg-containing sequences with phosphorodiester backbone an... 22613717 - Heterozygous carriage of a dysfunctional tlr9 allele affects cpg-oligonucleotide respon... 17215377 - A critical role for peptidoglycan n-deacetylation in listeria evasion from the host inn... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Cancer cell Volume: 19 ISSN: 1878-3686 ISO Abbreviation: Cancer Cell Publication Date: 2011 Apr |
Date Detail:
|
Created Date: 2011-04-12 Completed Date: 2011-06-07 Revised Date: 2012-04-18 |
Medline Journal Info:
|
Nlm Unique ID: 101130617 Medline TA: Cancer Cell Country: United States |
Other Details:
|
Languages: eng Pagination: 441-55 Citation Subset: IM |
Copyright Information:
|
Copyright © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
|
Diabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Acute Disease Adenocarcinoma / etiology*, pathology Adult Aged Aged, 80 and over Animals Carcinoma, Pancreatic Ductal / etiology*, pathology Disease Progression Female Genes, ras Humans Interleukin-6 / physiology Male Matrix Metalloproteinase 7 / blood, physiology* Mice Middle Aged Pancreatic Neoplasms / etiology*, pathology Pancreatitis / complications, pathology Proto-Oncogene Proteins p21(ras) / genetics STAT3 Transcription Factor / physiology* |
| Grant Support | |
ID/Acronym/Agency:
|
CA112537/CA/NCI NIH HHS; P30CA042014/CA/NCI NIH HHS; R01 CA112537-05/CA/NCI NIH HHS; R01 CA112537-06A1/CA/NCI NIH HHS; R01 CA112537-07/CA/NCI NIH HHS; R03 CA115225/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Interleukin-6; 0/STAT3 Transcription Factor; 0/STAT3 protein, human; 0/Stat3 protein, mouse; EC 3.4.24.23/Matrix Metalloproteinase 7; EC 3.6.5.2/Kras2 protein, mouse; EC 3.6.5.2/Proto-Oncogene Proteins p21(ras) |
| Comments/Corrections | |
Comment In:
|
Cancer Cell. 2011 Apr 12;19(4):429-31
[PMID:
21481782
]
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Resisting Targeted Therapy: Fifty Ways to Leave Your EGFR.
Next Document: Stat3/Socs3 activation by IL-6 transsignaling promotes progression of pancreatic intraepithelial neo...