Document Detail


Oncogenic Kras activates a hematopoietic-to-epithelial IL-17 signaling axis in preinvasive pancreatic neoplasia.
MedLine Citation:
PMID:  24823639     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Many human cancers are dramatically accelerated by chronic inflammation. However, the specific cellular and molecular elements mediating this effect remain largely unknown. Using a murine model of pancreatic intraepithelial neoplasia (PanIN), we found that Kras(G12D) induces expression of functional IL-17 receptors on PanIN epithelial cells and also stimulates infiltration of the pancreatic stroma by IL-17-producing immune cells. Both effects are augmented by associated chronic pancreatitis, resulting in functional in vivo changes in PanIN epithelial gene expression. Forced IL-17 overexpression dramatically accelerates PanIN initiation and progression, while inhibition of IL-17 signaling using genetic or pharmacologic techniques effectively prevents PanIN formation. Together, these studies suggest that a hematopoietic-to-epithelial IL-17 signaling axis is a potent and requisite driver of PanIN formation.
Authors:
Florencia McAllister; Jennifer M Bailey; Janivette Alsina; Christopher J Nirschl; Rajni Sharma; Hongni Fan; Yanique Rattigan; Jeffrey C Roeser; Rachana H Lankapalli; Hao Zhang; Elizabeth M Jaffee; Charles G Drake; Franck Housseau; Anirban Maitra; Jay K Kolls; Cynthia L Sears; Drew M Pardoll; Steven D Leach
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer cell     Volume:  25     ISSN:  1878-3686     ISO Abbreviation:  Cancer Cell     Publication Date:  2014 May 
Date Detail:
Created Date:  2014-05-14     Completed Date:  2014-07-15     Revised Date:  2014-08-11    
Medline Journal Info:
Nlm Unique ID:  101130617     Medline TA:  Cancer Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  621-37     Citation Subset:  IM    
Copyright Information:
Copyright © 2014 Elsevier Inc. All rights reserved.
Data Bank Information
Bank Name/Acc. No.:
GEO/GSE54753
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MeSH Terms
Descriptor/Qualifier:
Animals
Carcinoma in Situ / genetics,  metabolism,  prevention & control
Cell Transformation, Neoplastic
Chemoprevention
Epithelial Cells / metabolism*
Hematopoietic System / cytology,  metabolism*
Humans
Inflammation
Interleukin-17 / antagonists & inhibitors,  genetics,  metabolism*
Mice
Mice, Transgenic
Pancreas / pathology
Pancreatic Neoplasms / genetics,  metabolism*,  prevention & control
Proto-Oncogene Proteins p21(ras) / metabolism*
Receptors, Antigen, T-Cell, gamma-delta / biosynthesis,  metabolism
Receptors, Interleukin-17 / biosynthesis,  metabolism
Signal Transduction / genetics
Th17 Cells / immunology
Grant Support
ID/Acronym/Agency:
F32 CA157044/CA/NCI NIH HHS; F32 CA157044/CA/NCI NIH HHS; P01 CA134292/CA/NCI NIH HHS; P01 CA134292/CA/NCI NIH HHS; R01 DK097087/DK/NIDDK NIH HHS; S10 RR017933/RR/NCRR NIH HHS; T32 CA126607/CA/NCI NIH HHS; T32CA126607/CA/NCI NIH HHS; T32GM066691/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Il17a protein, mouse; 0/Interleukin-17; 0/Receptors, Antigen, T-Cell, gamma-delta; 0/Receptors, Interleukin-17; EC 3.6.5.2/Kras2 protein, mouse; EC 3.6.5.2/Proto-Oncogene Proteins p21(ras)
Comments/Corrections
Comment In:
Nat Rev Drug Discov. 2014 Jul;13(7):493   [PMID:  24981357 ]
Cancer Cell. 2014 May 12;25(5):553-4   [PMID:  24823632 ]

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